# NM_005502.4(ABCA1):c.6450G>A (p.Pro2150=)

https://sugi.bio/variant/abca1-p-pro2150

## Summary

**ABCA1 p.Pro2150= (c.6450G>A)** is classified **Benign/Likely benign** in ABCA1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.8%, afr); Associated with Cardiovascular phenotype.

**At a glance:** Benign/Likely benign · review: Multiple submitters · rsID rs61741359 · 7 submitters · 3 linked conditions · low-frequency (popmax 3.8%, afr)

## For patients & families {#patients}

This is a change in the ABCA1 gene that is classified as benign/likely benign — not considered disease-causing, submitted by 7 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 | [ABCA1](https://sugi.bio/atlas/gene/ABCA1/) |
| Protein change (HGVS p.) | p.Pro2150= |
| Coding change (HGVS c.) | c.6450G>A |
| MANE Select transcript | [NM_018376](https://www.ncbi.nlm.nih.gov/nuccore/NM_018376) (variant reported on NM_005502) |
| dbSNP | [rs61741359](https://www.ncbi.nlm.nih.gov/snp/rs61741359/) |
| Variant type | single nucleotide variant |
| Location | chr9:104785591-104785591 (GRCh38) |
| ClinVar | [VCV364378](https://www.ncbi.nlm.nih.gov/clinvar/variation/364378/) |

**All HGVS expressions:** `LRG_542:g.147565G>A`, `LRG_542t1:c.6450G>A`, `NC_000009.11:g.107547872C>T`, `NC_000009.12:g.104785591C>T`, `NG_007981.1:g.147565G>A`, `NM_005502.4:c.6450G>A`

## 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 0.021, GERP -4.24, phastCons 0.036 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 9.624**. 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 **3.8%** (afr) · FAF95 3.69% · FAF99 3.64% · 2,852/75,016 in the highest group · 3,226/1,614,088 alleles overall — low-frequency (popmax 3.8%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 3.8% | 26 |
| Admixed American | 0.305% | 328 |
| Remaining individuals (not grpmax-eligible) | 0.214% | 466 |
| Middle Eastern | 0.116% | 866 |
| South Asian | 0.0121% | 8,278 |
| European (non-Finnish) | 0.00331% | 30,257 |

*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}

**Benign/Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2026-02-01.

**Submitter consensus:** conflicting (6 Benign, 2 Likely benign).

**Submission history:** 8 submissions (2017–2026); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Illumina Laboratory Services, Illumina | Benign | criteria provided, single submitter | clinical testing | 2018-01-13 |
| Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Benign | criteria provided, single submitter | clinical testing | 2017-10-23 |
| GeneDx | Likely benign | criteria provided, single submitter | clinical testing | 2021-04-01 |
| Ambry Genetics | Benign | criteria provided, single submitter | clinical testing | 2020-03-19 |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2026-02-01 |
| Breakthrough Genomics, Breakthrough Genomics | Likely benign | criteria provided, single submitter | not provided |  |
| Mayo Clinic Laboratories, Mayo Clinic | Benign | criteria provided, single submitter | clinical testing | 2021-08-06 |

## Associated conditions {#conditions}

[Cardiovascular phenotype](https://sugi.bio/atlas/disease/cardiovascular-phenotype/), [Tangier disease](https://sugi.bio/atlas/disease/tangier-disease/), [hypoalphalipoproteinemia, primary, 1](https://sugi.bio/atlas/disease/hypoalphalipoproteinemia-primary-1/).

**Reported phenotype names (ClinVar):** Cardiovascular phenotype, Tangier disease, Hypoalphalipoproteinemia, primary, 1, not specified, not provided, none provided, HIGH DENSITY LIPOPROTEIN DEFICIENCY, TANGIER TYPE, HIGH DENSITY LIPOPROTEIN DEFICIENCY, TYPE 1, Cholesterol thesaurismosis, 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 364378). 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.*