Is ABCA3 p.Val563Ile (c.1687G>A) pathogenic?

ABCA3 p.Val563Ile (c.1687G>A) is classified Likely benign in ABCA3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1197); Rare (popmax 0.413%, sas); Associated with interstitial lung disease due to ABCA3 deficiency.

What condition is associated with ABCA3 p.Val563Ile (c.1687G>A)?

ABCA3 p.Val563Ile (c.1687G>A) is associated with interstitial lung disease due to ABCA3 deficiency, hereditary pulmonary alveolar proteinosis (ClinVar).

How common is ABCA3 p.Val563Ile (c.1687G>A) in the general population?

ABCA3 p.Val563Ile (c.1687G>A) is rare (popmax 0.413%, sas) (gnomAD).

What do computational predictors say about ABCA3 p.Val563Ile (c.1687G>A)?

AlphaMissense predicts likely benign (score 0.1197) — an in-silico prediction, not a clinical call.

ABCA3 p.Val563Ile

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.1687G>A · rs570927625 · VCV888168

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1197 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.413%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

interstitial lung disease due to ABCA3 deficiency

Computational evidence

Protein change
AlphaMissense	0.1197	likely benign
REVEL	0.474	indeterminate
SaProt	LLR -9.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.39, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	22.0	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 0.413% South Asian · 376/91,084 alleles

Filtering AF 0.378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.365%

Overall 0.0258% 417/1,613,890 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.413%	242
Remaining individualsnot grpmax-eligible	0.0224%	4,464
Finnishnot grpmax-eligible	0.0047%	21,277
East Asian	0.00223%	44,862
European (non-Finnish)	0.00186%	53,636
African / African-American	0.00133%	75,020

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.Val563Ile
Coding: c.1687G>A
MANE Select: NM_001089
dbSNP: rs570927625
Type: single nucleotide variant
Location: chr16:2299457 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 563: 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

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 p.Val563= Likely benign ★ same residue
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

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-val563ile (accessed [today's date]).

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