Is ABCA3 p.Ala131= (c.393C>T) pathogenic?

ABCA3 p.Ala131= (c.393C>T) is classified Conflicting classifications of pathogenicity in ABCA3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-20). Rare (popmax 0.198%, nfe); Associated with interstitial lung disease due to ABCA3 deficiency.

What condition is associated with ABCA3 p.Ala131= (c.393C>T)?

ABCA3 p.Ala131= (c.393C>T) is associated with interstitial lung disease due to ABCA3 deficiency, hereditary pulmonary alveolar proteinosis (ClinVar).

How common is ABCA3 p.Ala131= (c.393C>T) in the general population?

ABCA3 p.Ala131= (c.393C>T) is rare (popmax 0.198%, nfe) (gnomAD).

ABCA3 p.Ala131=

Q: How is Interstitial lung disease due to ABCA3 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.393C>T · rs145383120 · VCV712624

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.198%, nfe)

Conditions

interstitial lung disease due to ABCA3 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9	GERP -3.4
Overall
CADD	5.158	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.198% European (non-Finnish) · 2,332/1,179,802 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.188%

Overall 0.157% 2,534/1,609,580 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.198%	506
Admixed American	0.139%	722
Remaining individualsnot grpmax-eligible	0.13%	771
Middle Eastern	0.0495%	2,020
African / African-American	0.0387%	2,586
South Asian	0.0055%	18,172
Finnishnot grpmax-eligible	0.00166%	60,166

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.Ala131=
Coding: c.393C>T
MANE Select: NM_001089
dbSNP: rs145383120
Type: single nucleotide variant
Location: chr16:2324458 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 131: a β-strand

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

Disease context

interstitial lung disease due to ABCA3 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary pulmonary alveolar proteinosis

For Interstitial lung disease due to ABCA3 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

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-ala131 (accessed [today's date]).

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