Is ABCA1 p.Phe1971Ser (c.5912T>C) pathogenic?

ABCA1 p.Phe1971Ser (c.5912T>C) is classified Uncertain significance in ABCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-14). AlphaMissense: ambiguous (0.4638); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Phe1971Ser (c.5912T>C)?

ABCA1 p.Phe1971Ser (c.5912T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Phe1971Ser (c.5912T>C) in the general population?

ABCA1 p.Phe1971Ser (c.5912T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA1 p.Phe1971Ser (c.5912T>C)?

AlphaMissense predicts ambiguous (score 0.4638) — an in-silico prediction, not a clinical call.

ABCA1 p.Phe1971Ser

c.5912T>C · rs2538045659 · VCV2568289

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4638 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4638	ambiguous
REVEL	0.413	indeterminate
SaProt	LLR -10.36	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP -0.62, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 22 kb · p 3.8e-10 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCA1
Protein: p.Phe1971Ser
Coding: c.5912T>C
MANE Select: NM_005502
dbSNP: rs2538045659
Type: single nucleotide variant
Location: chr9:104790937 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 1971: the abc transporter 2 domain; a β-strand

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-phe1971ser (accessed [today's date]).

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