Is ABCA2 p.Arg1298His (c.3893G>A) pathogenic?

ABCA2 p.Arg1298His (c.3893G>A) is classified Likely benign in ABCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-23). AlphaMissense: likely benign (0.0545); Ultra-rare (popmax 0.0243%, amr).

How common is ABCA2 p.Arg1298His (c.3893G>A) in the general population?

ABCA2 p.Arg1298His (c.3893G>A) is ultra-rare (popmax 0.0243%, amr) (gnomAD).

What do computational predictors say about ABCA2 p.Arg1298His (c.3893G>A)?

AlphaMissense predicts likely benign (score 0.0545) — an in-silico prediction, not a clinical call.

ABCA2 p.Arg1298His

c.3893G>A · rs370357831 · VCV2250898

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0545 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0243%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0545	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.37	GERP -3
Regional constraint	o/e 1.04	unconstrained · MANE · 1,453 bp · p 0.54 · regional, not allelic
Overall
CADD	10.62	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 R1297H vs ClinVar R1298H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0243% Admixed American · 14/57,686 alleles

Filtering AF 0.0146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0117%

Overall 0.00331% 53/1,600,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0243%	4,120
South Asian	0.0102%	9,846
East Asian	0.00675%	14,821
Remaining individualsnot grpmax-eligible	0.00483%	20,685
European (non-Finnish)	0.00204%	48,939

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.Arg1298His
Coding: c.3893G>A
MANE Select: NM_001606
dbSNP: rs370357831
Type: single nucleotide variant
Location: chr9:137014800 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 1298: 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.Arg1298Leu 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-arg1298his (accessed [today's date]).

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