Is ABCA1 p.Ala937Val (c.2810C>T) pathogenic?

ABCA1 p.Ala937Val (c.2810C>T) is classified Pathogenic in ABCA1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1999-08-01). AlphaMissense: likely pathogenic (0.9848); Very rare (popmax 0.00329%, sas); Associated with Tangier disease.

What condition is associated with ABCA1 p.Ala937Val (c.2810C>T)?

ABCA1 p.Ala937Val (c.2810C>T) is associated with Tangier disease (ClinVar).

How common is ABCA1 p.Ala937Val (c.2810C>T) in the general population?

ABCA1 p.Ala937Val (c.2810C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

How is Tangier disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCA1 p.Ala937Val (c.2810C>T)?

AlphaMissense predicts likely pathogenic (score 0.9848) — an in-silico prediction, not a clinical call.

ABCA1 p.Ala937Val

c.2810C>T · rs137854495 · VCV9489

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9848 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Tangier disease

Computational evidence

Protein change
AlphaMissense	0.9848	likely pathogenic ✓ concordant with ClinVar · top 10% in ABCA1
REVEL	0.856	moderately pathogenic-leaning
SaProt	LLR -13.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.021 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,064 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000248% 4/1,613,546 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,355
European (non-Finnish)	8.47e-05%	1,179,949

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCA1
Protein: p.Ala937Val
Coding: c.2810C>T
MANE Select: NM_005502
dbSNP: rs137854495
Type: single nucleotide variant
Location: chr9:104822514 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 937: the abc transporter 1 domain; a β-strand; a binding site; a UniProt-annotated variant site (in tgd)

Full ABCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Tangier disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Tangier disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal

Similar variants

ABCA1 p.Ala937= Likely benign ★ same residue
ABCA1 p.Arg2080Trp Likely pathogenic ★★ same condition
ABCA1 p.Arg587Trp Pathogenic/Likely pathogenic ★★ same condition
ABCA1 p.Asn1800His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCA1 c.*2330A>T Uncertain significance ★★ same condition
ABCA1 c.*379C>T Uncertain significance ★★ same condition
ABCA1 p.Arg126Cys Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1342Trp Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abca1-p-ala937val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown