Is ABCA3 p.Leu39Val (c.115C>G) pathogenic?

ABCA3 p.Leu39Val (c.115C>G) is classified Conflicting classifications of pathogenicity in ABCA3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.3345); Rare (popmax 0.147%, eas); Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with ABCA3 p.Leu39Val (c.115C>G)?

ABCA3 p.Leu39Val (c.115C>G) is associated with hereditary pulmonary alveolar proteinosis (ClinVar).

How common is ABCA3 p.Leu39Val (c.115C>G) in the general population?

ABCA3 p.Leu39Val (c.115C>G) is rare (popmax 0.147%, eas) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

What do computational predictors say about ABCA3 p.Leu39Val (c.115C>G)?

AlphaMissense predicts likely benign (score 0.3345) — an in-silico prediction, not a clinical call.

ABCA3 p.Leu39Val

c.115C>G · rs200090198 · VCV2075268

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.3345 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.147%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary pulmonary alveolar proteinosis

Computational evidence

Protein change
AlphaMissense	0.3345	likely benign
REVEL	0.88	moderately pathogenic-leaning
SaProt	LLR -8.89	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 3	GERP -0.34, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 40 kb · p 0.47 · regional, not allelic
Overall
CADD	21.5	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 0.147% East Asian · 66/44,890 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.00663% 107/1,614,068 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.147%	680
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0128%	7,813
South Asian	0.00878%	11,386
European (non-Finnish)	0.00186%	53,639
African / African-American	0.00133%	75,042

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.Leu39Val
Coding: c.115C>G
MANE Select: NM_001089
dbSNP: rs200090198
Type: single nucleotide variant
Location: chr16:2326214 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 39: an α-helix

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

Disease context

hereditary pulmonary alveolar proteinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary pulmonary alveolar proteinosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

ABCA3 p.Leu39Phe Uncertain significance ★★ ⚠ same residue
ABCA3 p.Leu39Ile Uncertain significance ★ ⚠ same residue
ABCA3 c.2053-1G>C Likely pathogenic ★★ same condition
ABCA3 c.3863-98C>T Pathogenic ★★ same condition
ABCA3 p.Arg1550Trp Likely pathogenic ★★ same condition
ABCA3 p.Arg43Cys Pathogenic/Likely pathogenic ★★ same condition
ABCA3 p.Arg43His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCA3 p.Glu1540Lys 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-leu39val (accessed [today's date]).

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