Is ABCA3 p.His1247= (c.3741C>T) pathogenic?

ABCA3 p.His1247= (c.3741C>T) is classified Likely benign in ABCA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-25). Very rare (popmax 0.004%, afr); Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with ABCA3 p.His1247= (c.3741C>T)?

ABCA3 p.His1247= (c.3741C>T) is associated with hereditary pulmonary alveolar proteinosis (ClinVar).

How common is ABCA3 p.His1247= (c.3741C>T) in the general population?

ABCA3 p.His1247= (c.3741C>T) is very rare (popmax 0.004%, afr) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

ABCA3 p.His1247=

c.3741C>T · rs138817727 · VCV2885934

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 -3.7	GERP -4.2
Overall
CADD	0.589	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,928 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000929% 15/1,613,884 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,976
Admixed American	0.00167%	60,008
South Asian	0.0011%	91,090
European (non-Finnish)	0.000847%	118,002

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.His1247=
Coding: c.3741C>T
MANE Select: NM_001089
dbSNP: rs138817727
Type: single nucleotide variant
Location: chr16:2284400 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 1247: 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-his1247 (accessed [today's date]).

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