Is ABCA3 p.Phe71= (c.213C>T) pathogenic?

ABCA3 p.Phe71= (c.213C>T) is classified Benign/Likely benign in ABCA3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3.32%, eas); Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with ABCA3 p.Phe71= (c.213C>T)?

ABCA3 p.Phe71= (c.213C>T) is associated with hereditary pulmonary alveolar proteinosis, interstitial lung disease due to ABCA3 deficiency (ClinVar).

How common is ABCA3 p.Phe71= (c.213C>T) in the general population?

ABCA3 p.Phe71= (c.213C>T) is low-frequency (popmax 3.32%, eas) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

ABCA3 p.Phe71=

c.213C>T · rs117515055 · VCV318574

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.32%, eas)

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 -0.38	GERP -1.7, phastCons 0.004
Overall
CADD	7.823	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.32% East Asian · 1,488/44,882 alleles

Filtering AF 3.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.12%

Overall 0.106% 1,715/1,614,172 alleles · low-frequency exomes 1,527/1,461,814 · genomes 188/152,358 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	3.32%	30
Remaining individualsnot grpmax-eligible	0.256%	391
Middle Eastern	0.0495%	2,021
South Asian	0.0384%	2,603
African / African-American	0.0173%	5,774
Admixed American	0.00999%	10,005
European (non-Finnish)	0.000847%	118,005

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.Phe71=
Coding: c.213C>T
MANE Select: NM_001089
dbSNP: rs117515055
Type: single nucleotide variant
Location: chr16:2326116 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 71: a β-strand

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 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
ABCA3 p.Arg155Trp 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-phe71 (accessed [today's date]).

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