Is ABCA1 p.Ser1255Arg (c.3763A>C) pathogenic?

ABCA1 p.Ser1255Arg (c.3763A>C) is classified Likely benign in ABCA1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-31). AlphaMissense: ambiguous (0.4421); Rare (popmax 0.327%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Ser1255Arg (c.3763A>C)?

ABCA1 p.Ser1255Arg (c.3763A>C) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Ser1255Arg (c.3763A>C) in the general population?

ABCA1 p.Ser1255Arg (c.3763A>C) is rare (popmax 0.327%, afr) (gnomAD).

What do computational predictors say about ABCA1 p.Ser1255Arg (c.3763A>C)?

AlphaMissense predicts ambiguous (score 0.4421) — an in-silico prediction, not a clinical call.

ABCA1 p.Ser1255Arg

c.3763A>C · rs41436749 · VCV713117

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4421 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.327%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4421	ambiguous
REVEL	0.32	indeterminate
SaProt	LLR -8.75	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP -0.42, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.021 · regional, not allelic
Overall
CADD	24.0	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 0.327% African / African-American · 245/74,986 alleles

Filtering AF 0.293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.28%

Overall 0.0164% 265/1,614,056 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.327%	306
Middle Eastern	0.033%	3,031
Admixed American	0.015%	6,668
Remaining individualsnot grpmax-eligible	0.0144%	6,945

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.Ser1255Arg
Coding: c.3763A>C
MANE Select: NM_005502
dbSNP: rs41436749
Type: single nucleotide variant
Location: chr9:104814451 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB

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

Disease context

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

Similar variants

ABCA1 c.4175+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCA1 p.Thr940Met Pathogenic/Likely pathogenic ★★ same condition
ABCA1 c.3787+5C>A Uncertain significance ★★ same condition
ABCA1 p.Ala1855Ser Uncertain significance ★★ ⚠ same condition
ABCA1 p.Ala766Ser Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1283Cys Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1342Trp Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1417Cys 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-ser1255arg (accessed [today's date]).

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