Is ABCA3 p.Pro770Leu (c.2309C>T) pathogenic?

ABCA3 p.Pro770Leu (c.2309C>T) is classified Conflicting classifications of pathogenicity in ABCA3 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.0728); Rare (popmax 0.272%, nfe); Associated with interstitial lung disease due to ABCA3 deficiency.

What condition is associated with ABCA3 p.Pro770Leu (c.2309C>T)?

ABCA3 p.Pro770Leu (c.2309C>T) is associated with interstitial lung disease due to ABCA3 deficiency, hereditary pulmonary alveolar proteinosis (ClinVar).

How common is ABCA3 p.Pro770Leu (c.2309C>T) in the general population?

ABCA3 p.Pro770Leu (c.2309C>T) is rare (popmax 0.272%, nfe) (gnomAD).

What do computational predictors say about ABCA3 p.Pro770Leu (c.2309C>T)?

AlphaMissense predicts likely benign (score 0.0728) — an in-silico prediction, not a clinical call.

ABCA3 p.Pro770Leu

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.2309C>T · rs143929832 · VCV318489

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0728 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.272%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

interstitial lung disease due to ABCA3 deficiency

Computational evidence

Protein change
AlphaMissense	0.0728	likely benign
REVEL	0.667	pathogenic-leaning
SaProt	LLR -4.34	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -2.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	19.35	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 0.272% European (non-Finnish) · 3,208/1,180,044 alleles

Filtering AF 0.264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.261%

Overall 0.215% 3,476/1,614,070 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.272%	368
Remaining individualsnot grpmax-eligible	0.197%	508
Admixed American	0.08%	1,251
Middle Eastern	0.066%	1,516
African / African-American	0.0453%	2,208
Finnishnot grpmax-eligible	0.0391%	2,555
South Asian	0.0307%	3,253
East Asian	0.00891%	11,222
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803

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.Pro770Leu
Coding: c.2309C>T
MANE Select: NM_001089
dbSNP: rs143929832
Type: single nucleotide variant
Location: chr16:2295695 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 770: an α-helix

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.Pro770Gln Uncertain significance ★ ⚠ same residue
ABCA3 p.Pro770= 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

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-pro770leu (accessed [today's date]).

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