Is ABCA3 p.Asp731fs (c.2188_2189dup) pathogenic?

ABCA3 p.Asp731fs (c.21882189dup) is classified Pathogenic/Likely pathogenic in ABCA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-13). Absent from gnomAD; Associated with interstitial lung disease due to ABCA3 deficiency.

What condition is associated with ABCA3 p.Asp731fs (c.2188_2189dup)?

ABCA3 p.Asp731fs (c.2188_2189dup) is associated with interstitial lung disease due to ABCA3 deficiency (ClinVar).

How common is ABCA3 p.Asp731fs (c.2188_2189dup) in the general population?

ABCA3 p.Asp731fs (c.2188_2189dup) is absent from gnomAD (gnomAD).

ABCA3 p.Asp731fs

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.2188_2189dup · rs2505639879 · VCV2862508

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -5.4, phastCons 0.001

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCA3
Protein: p.Asp731fs
Coding: c.2188_2189dup
MANE Select: NM_001089
dbSNP: rs2505639879
Type: Duplication
Location: chr16:2297402 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 731: a β-strand; the abc transporter 1 domain

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

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

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ABCA3 p.Tyr492fs Pathogenic/Likely pathogenic ★★ same condition
ABCA3 c.873+84dup Benign ★★ same condition
ABCA3 p.Asn1519fs Likely pathogenic ★ same condition
ABCA3 p.Gly429fs Likely pathogenic ★ same condition
ABCA3 p.His1445fs Likely pathogenic ★ same condition
ABCA3 c.1112-20G>A Likely pathogenic ★★ same condition
ABCA3 c.2414+1G>A Likely pathogenic ★★ same condition
ABCA3 c.3863-98C>T 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-asp731fs (accessed [today's date]).

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