# NM_054027.6(ANKH):c.204C>T (p.Asp68=)

https://sugi.bio/variant/ankh-p-asp68

## Summary

**ANKH p.Asp68= (c.204C>T)** is classified **Likely benign** in ANKH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). Very rare (popmax 0.00167%, amr).

**At a glance:** Likely benign · review: Single submitter · rsID rs1434540901 · 1 submitter · very rare (popmax 0.00167%, amr)

## For patients & families {#patients}

This is a change in the ANKH gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*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 | [ANKH](https://sugi.bio/atlas/gene/ANKH/) |
| Protein change (HGVS p.) | p.Asp68= |
| Coding change (HGVS c.) | c.204C>T |
| MANE Select transcript | [NM_054027](https://www.ncbi.nlm.nih.gov/nuccore/NM_054027) |
| dbSNP | [rs1434540901](https://www.ncbi.nlm.nih.gov/snp/rs1434540901/) |
| Variant type | single nucleotide variant |
| Location | chr5:14769084-14769084 (GRCh38) |
| ClinVar | [VCV3017758](https://www.ncbi.nlm.nih.gov/clinvar/variation/3017758/) |

**All HGVS expressions:** `LRG_1362:g.107702C>T`, `LRG_1362t1:c.204C>T`, `NC_000005.10:g.14769084G>A`, `NC_000005.9:g.14769193G>A`, `NG_008273.2:g.107702C>T`, `NM_054027.6:c.204C>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 8.556, GERP 2.57, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 13.74**. 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: **below the reporting threshold**. This position is scored for a different substitution (G>C, Δ0.42 donor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.00167%** (amr) · 1/60,012 in the highest group · 1/1,461,892 alleles overall — very rare (popmax 0.00167%, amr).

*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.*

## Gene constraint & dosage {#gene-context}

**ANKH** population constraint: LOEUF 0.463, pLI 0.99706, missense-Z 3.5436; ClinGen dosage — haploinsufficiency 0, triplosensitivity 0 (0–3 scale). *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 84.57, 44% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of ANKH (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** ANKH's established molecular role includes phosphate transmembrane transporter activity.


### Pathways affected {#pathways}

ANKH participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Miscellaneous transport and binding events](https://reactome.org/content/detail/R-HSA-5223345) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** phosphate transmembrane transporter activity, ATP transmembrane transporter activity, transmembrane transporter activity.

**Biological process:** ATP export.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-12-22.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2023-12-22 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related ANKH variant pages (same residue, condition, or type): [ANKH c.1142-4A>G](/variant/ankh-c-1142-minus-4a-g), [ANKH c.96+5G>A](/variant/ankh-c-96-plus-5g-a), [ANKH c.*3752G>A](/variant/ankh-c-star-3752g-a), [ANKH p.Ala136Thr](/variant/ankh-p-ala136thr), [ANKH p.Ala201Thr](/variant/ankh-p-ala201thr), [ANKH p.Ala448Thr](/variant/ankh-p-ala448thr), [ANKH p.Arg453Gln](/variant/ankh-p-arg453gln), [ANKH p.Asn306Asp](/variant/ankh-p-asn306asp).

### 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 3017758). 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.*