Is ABCA2 p.Arg926Trp (c.2776C>T) pathogenic?

ABCA2 p.Arg926Trp (c.2776C>T) is classified Uncertain significance in ABCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: likely pathogenic (0.7661); Very rare (popmax 0.000173%, nfe); Associated with ABCA2-related disorder.

What condition is associated with ABCA2 p.Arg926Trp (c.2776C>T)?

ABCA2 p.Arg926Trp (c.2776C>T) is associated with ABCA2-related disorder (ClinVar).

How common is ABCA2 p.Arg926Trp (c.2776C>T) in the general population?

ABCA2 p.Arg926Trp (c.2776C>T) is very rare (popmax 0.000173%, nfe) (gnomAD).

What do computational predictors say about ABCA2 p.Arg926Trp (c.2776C>T)?

AlphaMissense predicts likely pathogenic (score 0.7661) — an in-silico prediction, not a clinical call.

ABCA2 p.Arg926Trp

c.2776C>T · VCV3362789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7661 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000173%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ABCA2-related disorder

Computational evidence

Protein change
AlphaMissense	0.7661	likely pathogenic
REVEL	0.585	indeterminate
SaProt	LLR -13.04	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -3.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 609 bp · p 0.15 · regional, not allelic
Overall
CADD	33.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R925W vs ClinVar R926W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000173% European (non-Finnish) · 2/1,154,980 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000142% 2/1,408,774 alleles · very rare

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: ABCA2
Protein: p.Arg926Trp
Coding: c.2776C>T
MANE Select: NM_001606
Type: single nucleotide variant
Location: chr9:137016721 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 926: a UniProt-annotated variant site (in idpogsa)

Full ABCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCA2-related disorder

Similar variants

ABCA2 p.Gln1370Ter Likely pathogenic ★★ same condition
ABCA2 p.Ala1357Thr Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg2392Gln Uncertain significance ★★ ⚠ same condition
ABCA2 p.Glu1515Lys Uncertain significance ★★ ⚠ same condition
ABCA2 p.Ser1427Arg Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg2298Trp Uncertain significance ★ ⚠ same condition
ABCA2 p.Thr398Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
ABCA2 c.6495+3G>A 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/abca2-p-arg926trp (accessed [today's date]).

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