Is ABCA2 p.Asp2433Asn (c.7297G>A) pathogenic?

ABCA2 p.Asp2433Asn (c.7297G>A) is classified Uncertain significance in ABCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-27). AlphaMissense: likely benign (0.2787); Ultra-rare (popmax 0.0283%, amr).

How common is ABCA2 p.Asp2433Asn (c.7297G>A) in the general population?

ABCA2 p.Asp2433Asn (c.7297G>A) is ultra-rare (popmax 0.0283%, amr) (gnomAD).

What do computational predictors say about ABCA2 p.Asp2433Asn (c.7297G>A)?

AlphaMissense predicts likely benign (score 0.2787) — an in-silico prediction, not a clinical call.

ABCA2 p.Asp2433Asn

c.7297G>A · rs771105113 · VCV2213943

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2787 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2787	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 1,110 bp · p 0.87 · regional, not allelic
Overall
CADD	26.7	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 D2432N vs ClinVar D2433N) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0283% Admixed American · 17/59,974 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00131% 21/1,605,616 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0283%	3,528
Remaining individualsnot grpmax-eligible	0.00321%	31,179
European (non-Finnish)	0.00017%	589,936

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.Asp2433Asn
Coding: c.7297G>A
MANE Select: NM_001606
dbSNP: rs771105113
Type: single nucleotide variant
Location: chr9:137007943 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 2433: a UniProt-annotated variant site (in idpogsa)

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-asp2433asn (accessed [today's date]).

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