Is ABCA3 p.Arg732His (c.2195G>A) pathogenic?

ABCA3 p.Arg732His (c.2195G>A) is classified Uncertain significance in ABCA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-09). AlphaMissense: likely benign (0.3246); Ultra-rare (popmax 0.017%, mid).

How common is ABCA3 p.Arg732His (c.2195G>A) in the general population?

ABCA3 p.Arg732His (c.2195G>A) is ultra-rare (popmax 0.017%, mid) (gnomAD).

What do computational predictors say about ABCA3 p.Arg732His (c.2195G>A)?

AlphaMissense predicts likely benign (score 0.3246) — an in-silico prediction, not a clinical call.

ABCA3 p.Arg732His

c.2195G>A · rs751006761 · VCV1910896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3246 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3246	likely benign
REVEL	0.703	pathogenic-leaning
SaProt	LLR -14.33	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.017% Middle Eastern · 1/5,898 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000744% 12/1,613,384 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.017%	5,898
Admixed American	0.00333%	29,991
African / African-American	0.00134%	74,878
South Asian	0.0011%	91,070
European (non-Finnish)	0.000593%	168,573

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: ABCA3
Protein: p.Arg732His
Coding: c.2195G>A
MANE Select: NM_001089
dbSNP: rs751006761
Type: single nucleotide variant
Location: chr16:2297397 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 732: a β-strand; the abc transporter 1 domain

Full ABCA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA3 c.1112-20G>A Likely pathogenic ★★ same type
ABCA3 c.2053-1G>C Likely pathogenic ★★ same type
ABCA3 c.2414+1G>A Likely pathogenic ★★ same type
ABCA3 c.3863-98C>T Pathogenic ★★ same type
ABCA3 c.614-2A>G Likely pathogenic ★★ same type
ABCA3 p.Ala1070Thr Likely pathogenic ★★ ⚠ same type
ABCA3 p.Arg1550Trp Likely pathogenic ★★ same type
ABCA3 p.Arg155Trp Likely pathogenic ★★ 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/abca3-p-arg732his (accessed [today's date]).

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