Is ABCA1 p.Ala1291Val (c.3872C>T) pathogenic?

ABCA1 p.Ala1291Val (c.3872C>T) is classified Uncertain significance in ABCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-17). AlphaMissense: likely benign (0.0591); Very rare (popmax 0.00167%, amr).

How common is ABCA1 p.Ala1291Val (c.3872C>T) in the general population?

ABCA1 p.Ala1291Val (c.3872C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ABCA1 p.Ala1291Val (c.3872C>T)?

AlphaMissense predicts likely benign (score 0.0591) — an in-silico prediction, not a clinical call.

ABCA1 p.Ala1291Val

c.3872C>T · rs1831520438 · VCV1467071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0591 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0591	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -6.08	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 3.5	GERP -3.6, phastCons 0.021
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.021 · regional, not allelic
Overall
CADD	6.195	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Overall 0.000124% 2/1,614,088 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Ala1291Val
Coding: c.3872C>T
MANE Select: NM_005502
dbSNP: rs1831520438
Type: single nucleotide variant
Location: chr9:104814147 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 1291: the 'disordered' region

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

Similar variants

ABCA1 p.Ala1291= Likely benign ★ same residue
ABCA1 c.4175+1G>T Pathogenic/Likely pathogenic ★★ same type
ABCA1 c.4274+1G>A Likely pathogenic ★★ same type
ABCA1 c.5237+3A>C Likely pathogenic ★★ same type
ABCA1 p.Arg2080Trp Likely pathogenic ★★ same type
ABCA1 p.Arg557Ter Pathogenic/Likely pathogenic ★★ same type
ABCA1 p.Arg587Trp Pathogenic/Likely pathogenic ★★ same type
ABCA1 p.Asn1800His Pathogenic/Likely pathogenic ★★ ⚠ same type

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-ala1291val (accessed [today's date]).

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