Is ABCA1 p.Ser2182Phe (c.6545C>T) pathogenic?

ABCA1 p.Ser2182Phe (c.6545C>T) is classified Conflicting classifications of pathogenicity in ABCA1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-26). AlphaMissense: likely benign (0.2648); Ultra-rare (popmax 0.0708%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Ser2182Phe (c.6545C>T)?

ABCA1 p.Ser2182Phe (c.6545C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Ser2182Phe (c.6545C>T) in the general population?

ABCA1 p.Ser2182Phe (c.6545C>T) is ultra-rare (popmax 0.0708%, afr) (gnomAD).

What do computational predictors say about ABCA1 p.Ser2182Phe (c.6545C>T)?

AlphaMissense predicts likely benign (score 0.2648) — an in-silico prediction, not a clinical call.

ABCA1 p.Ser2182Phe

c.6545C>T · rs369476391 · VCV1696271

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2648 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0708%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2648	likely benign
REVEL	0.483	indeterminate
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 22 kb · p 3.8e-10 · regional, not allelic
Overall
CADD	29.2	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 0.0708% African / African-American · 52/73,460 alleles

Filtering AF 0.0554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0499%

Overall 0.00349% 55/1,577,838 alleles · ultra-rare exomes 28/1,426,434 · genomes 27/151,404 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0708%	1,413
Remaining individualsnot grpmax-eligible	0.00335%	29,887
European (non-Finnish)	8.64e-05%	1,157,776

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.Ser2182Phe
Coding: c.6545C>T
MANE Select: NM_005502
dbSNP: rs369476391
Type: single nucleotide variant
Location: chr9:104785496 (GRCh38)

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

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-ser2182phe (accessed [today's date]).

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