Is ABCA3 p.Phe353= (c.1059C>T) pathogenic?

ABCA3 p.Phe353= (c.1059C>T) is classified Benign in ABCA3 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 39%, eas) — too common for a highly-penetrant pathogenic allele; Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with ABCA3 p.Phe353= (c.1059C>T)?

ABCA3 p.Phe353= (c.1059C>T) is associated with hereditary pulmonary alveolar proteinosis, interstitial lung disease due to ABCA3 deficiency (ClinVar).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

ABCA3 p.Phe353=

Q: How common is ABCA3 p.Phe353= (c.1059C>T) in the general population?

ABCA3 p.Phe353= (c.1059C>T) is common (popmax 39%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1059C>T · rs13332514 · VCV178698

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 39%, eas) — too common for a highly-penetrant pathogenic allele

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 -4.2	GERP -5.4
Overall
CADD	2.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 39% East Asian · 17,472/44,840 alleles

Filtering AF 38.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 38.3%

Overall 12.1% 195,277/1,613,880 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	39%	3
Admixed American	36.2%	3
South Asian	17.4%	6
Remaining individualsnot grpmax-eligible	12.4%	8
Middle Eastern	12%	8
Ashkenazi Jewishnot grpmax-eligible	11.2%	9
European (non-Finnish)	9.83%	10
Finnishnot grpmax-eligible	9.31%	11
African / African-American	8.51%	12
Amishnot grpmax-eligible	4.61%	22

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.Phe353=
Coding: c.1059C>T
MANE Select: NM_001089
dbSNP: rs13332514
Type: single nucleotide variant
Location: chr16:2317335 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 353: 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

Also linked: interstitial lung disease due to ABCA3 deficiency

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.Phe353Leu Uncertain significance ★ ⚠ 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
ABCA3 p.Arg1550Trp 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-phe353 (accessed [today's date]).

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