Is ABCA2 p.Arg288Trp (c.862C>T) pathogenic?

ABCA2 p.Arg288Trp (c.862C>T) is classified Uncertain significance in ABCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). AlphaMissense: likely benign (0.129); Ultra-rare (popmax 0.0933%, amr).

How common is ABCA2 p.Arg288Trp (c.862C>T) in the general population?

ABCA2 p.Arg288Trp (c.862C>T) is ultra-rare (popmax 0.0933%, amr) (gnomAD).

What do computational predictors say about ABCA2 p.Arg288Trp (c.862C>T)?

AlphaMissense predicts likely benign (score 0.129) — an in-silico prediction, not a clinical call.

ABCA2 p.Arg288Trp

c.862C>T · rs199818600 · VCV2580668

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.129 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0933%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.129	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -5.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -0.19, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,023 bp · p 0.16 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 R287W vs ClinVar R288W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0933% Admixed American · 56/60,008 alleles

Filtering AF 0.0737% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0667%

Overall 0.00559% 90/1,610,750 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0933%	1,072
East Asian	0.0424%	2,361
Remaining individualsnot grpmax-eligible	0.00801%	12,477
African / African-American	0.00666%	15,005
South Asian	0.0011%	91,038
European (non-Finnish)	0.000339%	294,961

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.Arg288Trp
Coding: c.862C>T
MANE Select: NM_001606
dbSNP: rs199818600
Type: single nucleotide variant
Location: chr9:137021427 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46

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

Similar variants

ABCA2 p.Arg288Gln Uncertain significance ★ ⚠ same residue
ABCA2 p.Gln1370Ter Likely pathogenic ★★ same type
ABCA2 c.3883-3C>T Uncertain significance ★★ same type
ABCA2 p.Ala1357Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1620Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1645Val Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1715Ser Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala2180Thr 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/abca2-p-arg288trp (accessed [today's date]).

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