Is ABCA9 p.Ala1492Pro (c.4474G>C) pathogenic?

ABCA9 p.Ala1492Pro (c.4474G>C) is classified Uncertain significance in ABCA9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-30). AlphaMissense: likely pathogenic (0.9729); Absent from gnomAD v4.1.

How common is ABCA9 p.Ala1492Pro (c.4474G>C) in the general population?

ABCA9 p.Ala1492Pro (c.4474G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA9 p.Ala1492Pro (c.4474G>C)?

AlphaMissense predicts likely pathogenic (score 0.9729) — an in-silico prediction, not a clinical call.

ABCA9 p.Ala1492Pro

c.4474G>C · rs2509689390 · VCV2280893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9729 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9729	likely pathogenic · top 1% in ABCA9
REVEL	0.86	moderately pathogenic-leaning
SaProt	LLR -11.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 75 kb · p 0.014 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: ABCA9
Protein: p.Ala1492Pro
Coding: c.4474G>C
MANE Select: NM_080283
dbSNP: rs2509689390
Type: single nucleotide variant
Location: chr17:68984081 (GRCh38)
Gene constraint: LOEUF 1.006 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.22
Residue 1492: the abc transporter 2 domain

Full ABCA9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA9 p.Tyr1123= Likely benign ★★ same type
ABCA9 p.Ala1071Val Uncertain significance ★ ⚠ same type
ABCA9 p.Ala1153Thr Uncertain significance ★ ⚠ same type
ABCA9 p.Ala1196Thr Uncertain significance ★ ⚠ same type
ABCA9 p.Ala125Thr Uncertain significance ★ ⚠ same type
ABCA9 p.Ala1285Thr Uncertain significance ★ ⚠ same type
ABCA9 p.Ala1407Val Uncertain significance ★ ⚠ same type
ABCA9 p.Ala14Ser Uncertain significance ★ ⚠ 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/abca9-p-ala1492pro (accessed [today's date]).

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