Is ABCA2 p.Lys295Arg (c.884A>G) pathogenic?

ABCA2 p.Lys295Arg (c.884A>G) is classified Uncertain significance in ABCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: likely benign (0.0892); Rare (popmax 0.145%, eas).

How common is ABCA2 p.Lys295Arg (c.884A>G) in the general population?

ABCA2 p.Lys295Arg (c.884A>G) is rare (popmax 0.145%, eas) (gnomAD).

What do computational predictors say about ABCA2 p.Lys295Arg (c.884A>G)?

AlphaMissense predicts likely benign (score 0.0892) — an in-silico prediction, not a clinical call.

ABCA2 p.Lys295Arg

c.884A>G · rs556418656 · VCV3098594

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0892 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.145%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0892	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -5.56	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 0.85	GERP 0.29, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,023 bp · p 0.16 · regional, not allelic
Overall
CADD	12.6	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 K294R vs ClinVar K295R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.145% East Asian · 65/44,862 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.00429% 69/1,608,086 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.145%	690
Remaining individualsnot grpmax-eligible	0.0016%	62,318
European (non-Finnish)	0.000254%	393,258

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.Lys295Arg
Coding: c.884A>G
MANE Select: NM_001606
dbSNP: rs556418656
Type: single nucleotide variant
Location: chr9:137021405 (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.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
ABCA2 p.Ala2206Val 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-lys295arg (accessed [today's date]).

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