Is ABCA2 p.Arg2298Trp (c.6892C>T) pathogenic?

ABCA2 p.Arg2298Trp (c.6892C>T) is classified Uncertain significance in ABCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-21). AlphaMissense: likely benign (0.2945); Ultra-rare (popmax 0.0112%, nfe); Associated with ABCA2-related disorder.

What condition is associated with ABCA2 p.Arg2298Trp (c.6892C>T)?

ABCA2 p.Arg2298Trp (c.6892C>T) is associated with ABCA2-related disorder (ClinVar).

How common is ABCA2 p.Arg2298Trp (c.6892C>T) in the general population?

ABCA2 p.Arg2298Trp (c.6892C>T) is ultra-rare (popmax 0.0112%, nfe) (gnomAD).

What do computational predictors say about ABCA2 p.Arg2298Trp (c.6892C>T)?

AlphaMissense predicts likely benign (score 0.2945) — an in-silico prediction, not a clinical call.

ABCA2 p.Arg2298Trp

c.6892C>T · rs747266171 · VCV2634932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2945 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCA2-related disorder

Computational evidence

Protein change
AlphaMissense	0.2945	likely benign
REVEL	0.677	pathogenic-leaning
SaProt	LLR -9.97	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.28, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 1,110 bp · p 0.87 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R2297W vs ClinVar R2298W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% European (non-Finnish) · 131/1,173,758 alleles

Filtering AF 0.00958% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00901%

Overall 0.0088% 140/1,590,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0112%	8,960
South Asian	0.00443%	22,597
African / African-American	0.0042%	23,784
Finnishnot grpmax-eligible	0.00176%	56,720
Remaining individualsnot grpmax-eligible	0.00162%	61,858

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.Arg2298Trp
Coding: c.6892C>T
MANE Select: NM_001606
dbSNP: rs747266171
Type: single nucleotide variant
Location: chr9:137008989 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 2298: 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.Arg2298Gln Uncertain significance ★ ⚠ same residue
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.Arg926Trp Uncertain significance ★ ⚠ same condition
ABCA2 p.Thr398Lys Conflicting classifications of pathogenicity ★ ⚠ 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-arg2298trp (accessed [today's date]).

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