# NM_001148.6(ANK2):c.7236A>T (p.Ala2412=)

https://sugi.bio/variant/ank2-p-ala2412

## Summary

**ANK2 p.Ala2412= (c.7236A>T)** is classified **Likely benign** in ANK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-10). Very rare (popmax 0.000339%, nfe); Associated with Cardiovascular phenotype.

**At a glance:** Likely benign · review: Multiple submitters · rsID rs1394535709 · 3 submitters · 2 linked conditions · very rare (popmax 0.000339%, nfe)

## For patients & families {#patients}

This is a change in the ANK2 gene that is classified as likely benign — not considered disease-causing, submitted by 3 submitters, and is linked to Cardiovascular phenotype.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [ANK2](https://sugi.bio/atlas/gene/ANK2/) |
| Protein change (HGVS p.) | p.Ala2412= |
| Coding change (HGVS c.) | c.7236A>T |
| dbSNP | [rs1394535709](https://www.ncbi.nlm.nih.gov/snp/rs1394535709/) |
| Variant type | single nucleotide variant |
| Location | chr4:113355854-113355854 (GRCh38) |
| ClinVar | [VCV519317](https://www.ncbi.nlm.nih.gov/clinvar/variation/519317/) |

**All HGVS expressions:** `LRG_327:g.542772A>T`, `LRG_327t1:c.7236A>T`, `NC_000004.11:g.114277010A>T`, `NC_000004.12:g.113355854A>T`, `NG_009006.2:g.542772A>T`, `NM_001127493.3:c.4400-4969A>T`, `NM_001148.6:c.7236A>T`, `NM_001354225.2:c.4439-4969A>T`, `NM_001354228.2:c.4328-4969A>T`, `NM_001354230.2:c.4406-4969A>T`, `NM_001354231.2:c.4469-4969A>T`, `NM_001354232.2:c.4463-4969A>T`, `NM_001354235.2:c.4424-4969A>T`, `NM_001354236.2:c.4325-4969A>T`, `NM_001354237.2:c.4505-4969A>T`, `NM_001354239.2:c.4397-4969A>T`, `NM_001354240.2:c.4472-4969A>T`, `NM_001354241.2:c.4472-4969A>T`, `NM_001354242.2:c.4469-4969A>T`, `NM_001354243.2:c.4364-4969A>T`, `NM_001354244.2:c.4361-4969A>T`, `NM_001354245.2:c.4265-4969A>T`, `NM_001354246.2:c.4424-4969A>T`, `NM_001354249.2:c.4241-4969A>T`, `NM_001354252.2:c.4397-4969A>T`, `NM_001354253.2:c.4202-4969A>T`, `NM_001354254.2:c.4376-4969A>T`, `NM_001354255.2:c.4364-4969A>T`, `NM_001354256.2:c.4361-4969A>T`, `NM_001354257.2:c.4166-4969A>T`, `NM_001354258.2:c.4328-4969A>T`, `NM_001354260.2:c.4142-4969A>T`, `NM_001354261.2:c.4286-4969A>T`, `NM_001354262.2:c.4265-4969A>T`, `NM_001354264.2:c.4262-4969A>T`, `NM_001354265.2:c.4424-4969A>T`, `NM_001354266.2:c.4241-4969A>T`, `NM_001354267.2:c.4241-4969A>T`, `NM_001354268.2:c.4229-4969A>T`, `NM_001354269.3:c.4214-4969A>T`, `NM_001354270.2:c.4202-4969A>T`, `NM_001354271.2:c.4142-4969A>T`, `NM_001354272.2:c.4298-4969A>T`, `NM_001354273.2:c.4127-4969A>T`, `NM_001354274.2:c.4193-4969A>T`, `NM_001354275.2:c.4265-4969A>T`, `NM_001354276.2:c.4241-4969A>T`, `NM_001354277.2:c.4043-4969A>T`, `NM_001354278.2:c.1955-4969A>T`, `NM_001354279.2:c.1991-4969A>T`, `NM_001354280.2:c.1976-4969A>T`, `NM_001354281.2:c.1955-4969A>T`, `NM_001354282.2:c.1991-4969A>T`, `NM_001386142.1:c.7002A>T`, `NM_001386143.1:c.4364-4969A>T`, `NM_001386144.1:c.4472-4969A>T`, `NM_001386146.1:c.4208-4969A>T`, `NM_001386147.1:c.4253-4969A>T`, `NM_001386148.2:c.4412-4969A>T`, `NM_001386149.1:c.4208-4969A>T`, `NM_001386150.1:c.4208-4969A>T`, `NM_001386151.1:c.4142-4969A>T`, `NM_001386152.1:c.4484-4969A>T`, `NM_001386153.1:c.4208-4969A>T`, `NM_001386154.1:c.4193-4969A>T`, `NM_001386156.1:c.4166-4969A>T`, `NM_001386157.1:c.4043-4969A>T`, `NM_001386158.1:c.3944-4969A>T`, `NM_001386160.1:c.4271-4969A>T`, `NM_001386161.1:c.4361-4969A>T`, `NM_001386162.1:c.4241-4969A>T`, `NM_001386166.1:c.3636A>T`, `NM_001386167.1:c.827-4969A>T`, `NM_001386174.1:c.7377A>T`, `NM_001386175.1:c.7353A>T`, `NM_001386186.2:c.4412-4969A>T`, `NM_001386187.2:c.4292-4969A>T`, `NM_020977.5:c.4427-4969A>T`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP -2.167, GERP -5.72 — fast-evolving / accelerated position
- CADD: **PHRED 3.611**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **0.000339%** (nfe) · FAF95 7.9e-05% · FAF99 5.4e-05% · 4/1,179,930 in the highest group · 4/1,613,760 alleles overall — very rare (popmax 0.000339%, nfe).

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Clinical significance {#significance}

**Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2023-04-10.

**Submitter consensus:** unanimous (3/3 Likely benign).

**Submission history:** 3 submissions (2020–2023); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2020-12-02 |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2022-05-02 |
| Blueprint Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2023-04-10 |

## Associated conditions {#conditions}

[Cardiovascular phenotype](https://sugi.bio/atlas/disease/cardiovascular-phenotype/), [long QT syndrome](https://sugi.bio/atlas/disease/long-qt-syndrome/).

**Reported phenotype names (ClinVar):** Cardiovascular phenotype, Long QT syndrome, not specified, AllHighlyPenetrant.

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 519317). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*