Is ABCA9 p.Arg979Trp (c.2935C>T) pathogenic?

ABCA9 p.Arg979Trp (c.2935C>T) is classified Uncertain significance in ABCA9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). AlphaMissense: ambiguous (0.3572); Ultra-rare (popmax 0.0122%, afr).

How common is ABCA9 p.Arg979Trp (c.2935C>T) in the general population?

ABCA9 p.Arg979Trp (c.2935C>T) is ultra-rare (popmax 0.0122%, afr) (gnomAD).

What do computational predictors say about ABCA9 p.Arg979Trp (c.2935C>T)?

AlphaMissense predicts ambiguous (score 0.3572) — an in-silico prediction, not a clinical call.

ABCA9 p.Arg979Trp

c.2935C>T · VCV3529075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3572 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, afr)

Computational evidence

Protein change
AlphaMissense	0.3572	ambiguous
REVEL	0.527	indeterminate
SaProt	LLR -5.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -0.54, phastCons 0.001
Regional constraint	o/e 0.94	unconstrained · MANE · 75 kb · p 0.014 · regional, not allelic
Overall
CADD	19.76	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 0.0122% African / African-American · 9/73,908 alleles

Filtering AF 0.00631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00473%

Overall 0.00262% 42/1,600,924 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0122%	8,212
East Asian	0.00683%	14,645
South Asian	0.00563%	17,758
Admixed American	0.00351%	28,468
European (non-Finnish)	0.00179%	55,973
Remaining individualsnot grpmax-eligible	0.00161%	61,920
Finnishnot grpmax-eligible	0.00157%	63,788

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: ABCA9
Protein: p.Arg979Trp
Coding: c.2935C>T
MANE Select: NM_080283
Type: single nucleotide variant
Location: chr17:69016357 (GRCh38)
Gene constraint: LOEUF 1.006 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.22

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.Ala1492Pro 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-arg979trp (accessed [today's date]).

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