Is ABCA3 p.Glu292Val (c.875A>T) pathogenic?

ABCA3 p.Glu292Val (c.875A>T) is classified Pathogenic/Likely pathogenic in ABCA3 (ClinVar, Multiple submitters, 28 submitters; last evaluated 2026-02-18). AlphaMissense: likely pathogenic (0.7033); Rare (popmax 0.579%, nfe); Associated with ABCA3-related disorder.

What condition is associated with ABCA3 p.Glu292Val (c.875A>T)?

ABCA3 p.Glu292Val (c.875A>T) is associated with ABCA3-related disorder, hereditary pulmonary alveolar proteinosis, interstitial lung disease due to ABCA3 deficiency (ClinVar).

How common is ABCA3 p.Glu292Val (c.875A>T) in the general population?

ABCA3 p.Glu292Val (c.875A>T) is rare (popmax 0.579%, nfe) (gnomAD).

What do computational predictors say about ABCA3 p.Glu292Val (c.875A>T)?

AlphaMissense predicts likely pathogenic (score 0.7033) — an in-silico prediction, not a clinical call.

ABCA3 p.Glu292Val

c.875A>T · rs149989682 · VCV203381

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 28 submitters

AlphaMissense

likely pathogenic

0.7033 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.579%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCA3-related disorder

Computational evidence

Protein change
AlphaMissense	0.7033	likely pathogenic ✓ concordant with ClinVar
REVEL	0.949	strongly pathogenic-leaning
SaProt	LLR -7.95	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	31.0	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 0.579% European (non-Finnish) · 6,829/1,179,822 alleles

Filtering AF 0.567% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.563%

Overall 0.453% 7,316/1,613,934 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.75%	57
European (non-Finnish)grpmax	0.579%	173
Remaining individualsnot grpmax-eligible	0.386%	259
Admixed American	0.172%	583
African / African-American	0.0959%	1,043
Finnishnot grpmax-eligible	0.0719%	1,392
Middle Eastern	0.0166%	6,040
South Asian	0.00659%	15,181
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
East Asian	0.00223%	44,872

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu292Val
Coding: c.875A>T
MANE Select: NM_001089
dbSNP: rs149989682
Type: single nucleotide variant
Location: chr16:2317763 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 292: a UniProt-annotated variant site (in smdp3; uncertain significance; does not affect lamellar bodies membrane location; does not affect proteolytic cleavage; affects lamellar bodies formation; does not affect cholesterol and phosphatidylcholine transport; decreases vesicles formation; does not affect free cholesterol induced cell death); an α-helix

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

Disease context

ABCA3-related disorder

Also linked: hereditary pulmonary alveolar proteinosis interstitial lung disease due to ABCA3 deficiency interstitial lung disease 2

Similar variants

ABCA3 c.1112-20G>A Likely pathogenic ★★ same condition
ABCA3 c.2053-1G>C Likely pathogenic ★★ same condition
ABCA3 c.2414+1G>A Likely pathogenic ★★ same condition
ABCA3 c.3863-98C>T Pathogenic ★★ same condition
ABCA3 c.614-2A>G Likely pathogenic ★★ same condition
ABCA3 p.Ala1070Thr Likely pathogenic ★★ ⚠ same condition
ABCA3 p.Arg1550Trp Likely pathogenic ★★ same condition
ABCA3 p.Arg155Trp Likely pathogenic ★★ same condition

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-glu292val (accessed [today's date]).

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