Is ABCA3 p.Pro584Ser (c.1750C>T) pathogenic?

ABCA3 p.Pro584Ser (c.1750C>T) is classified Conflicting classifications of pathogenicity in ABCA3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-03-09). AlphaMissense: likely benign (0.112); Rare (popmax 0.412%, mid); Associated with interstitial lung disease due to ABCA3 deficiency.

What condition is associated with ABCA3 p.Pro584Ser (c.1750C>T)?

ABCA3 p.Pro584Ser (c.1750C>T) is associated with interstitial lung disease due to ABCA3 deficiency, hereditary pulmonary alveolar proteinosis (ClinVar).

How common is ABCA3 p.Pro584Ser (c.1750C>T) in the general population?

ABCA3 p.Pro584Ser (c.1750C>T) is rare (popmax 0.412%, mid) (gnomAD).

What do computational predictors say about ABCA3 p.Pro584Ser (c.1750C>T)?

AlphaMissense predicts likely benign (score 0.112) — an in-silico prediction, not a clinical call.

ABCA3 p.Pro584Ser

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.1750C>T · rs552751331 · VCV318503

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.112 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.412%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

interstitial lung disease due to ABCA3 deficiency

Computational evidence

Protein change
AlphaMissense	0.112	likely benign
REVEL	0.457	indeterminate
SaProt	LLR -8.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	23.7	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 0.412% Middle Eastern · 24/5,828 alleles

Filtering AF 0.284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.242%

Overall 0.0176% 284/1,613,462 alleles · rare exomes 260/1,461,156 · genomes 24/152,306 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.412%	243
South Asian	0.253%	396
Remaining individualsnot grpmax-eligible	0.0336%	2,975
African / African-American	0.00133%	75,046
European (non-Finnish)	0.000678%	147,501

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.Pro584Ser
Coding: c.1750C>T
MANE Select: NM_001089
dbSNP: rs552751331
Type: single nucleotide variant
Location: chr16:2298532 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 584: 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 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-pro584ser (accessed [today's date]).

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