Is ABCA1 p.Val771Met (c.2311G>A) pathogenic?

ABCA1 p.Val771Met (c.2311G>A) is classified Benign in ABCA1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1337); Common (popmax 12.9%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Tangier disease.

What condition is associated with ABCA1 p.Val771Met (c.2311G>A)?

ABCA1 p.Val771Met (c.2311G>A) is associated with Tangier disease, hypoalphalipoproteinemia, primary, 1 (ClinVar).

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.Val771Met (c.2311G>A)?

AlphaMissense predicts likely benign (score 0.1337) — an in-silico prediction, not a clinical call.

ABCA1 p.Val771Met

Q: How common is ABCA1 p.Val771Met (c.2311G>A) in the general population?

ABCA1 p.Val771Met (c.2311G>A) is common (popmax 12.9%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2311G>A · rs2066718 · VCV364433

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1337 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 12.9%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Tangier disease

Computational evidence

Protein change
AlphaMissense	0.1337	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.84, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 81 kb · p 0.081 · regional, not allelic
Overall
CADD	23.0	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 12.9% Admixed American · 7,736/60,020 alleles

Filtering AF 12.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.6%

Overall 3.94% 63,556/1,613,990 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	15.5%	6
Admixed Americangrpmax	12.9%	8
Middle Eastern	9.45%	11
African / African-American	9.21%	11
South Asian	6.39%	16
Ashkenazi Jewishnot grpmax-eligible	4.97%	20
Remaining individualsnot grpmax-eligible	4.7%	21
East Asian	4.08%	25
European (non-Finnish)	2.98%	34
Finnishnot grpmax-eligible	1.56%	64

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val771Met
Coding: c.2311G>A
MANE Select: NM_005502
dbSNP: rs2066718
Type: single nucleotide variant
Location: chr9:104826974 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 771: a UniProt-annotated variant site (in)

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

Also linked: hypoalphalipoproteinemia, primary, 1

For Tangier disease (Orphanet):

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

Similar variants

ABCA1 p.Val771Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA1 c.5237+3A>C Likely pathogenic ★★ same condition
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

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-val771met (accessed [today's date]).

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