Is ABCA3 p.Ala916= (c.2748C>T) pathogenic?

ABCA3 p.Ala916= (c.2748C>T) is classified Likely benign in ABCA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-28). Ultra-rare (popmax 0.0216%, amr); Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with ABCA3 p.Ala916= (c.2748C>T)?

ABCA3 p.Ala916= (c.2748C>T) is associated with hereditary pulmonary alveolar proteinosis (ClinVar).

How common is ABCA3 p.Ala916= (c.2748C>T) in the general population?

ABCA3 p.Ala916= (c.2748C>T) is ultra-rare (popmax 0.0216%, amr) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

ABCA3 p.Ala916=

c.2748C>T · rs768240890 · VCV1795506

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0216%, amr)

Conditions

hereditary pulmonary alveolar proteinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -5.1
Overall
CADD	7.716	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0216% Admixed American · 12/55,622 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00974%

Overall 0.00139% 22/1,580,640 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0216%	4,635
Middle Eastern	0.0165%	6,054
Remaining individualsnot grpmax-eligible	0.00163%	61,340
African / African-American	0.00134%	74,448
South Asian	0.00115%	87,248
European (non-Finnish)	0.000515%	194,131

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.Ala916=
Coding: c.2748C>T
MANE Select: NM_001089
dbSNP: rs768240890
Type: single nucleotide variant
Location: chr16:2288282 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 916: 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 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
ABCA3 p.Glu292Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCA3 p.Gly1459Asp 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-ala916 (accessed [today's date]).

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