Is SFTPB p.Val63= (c.189G>A) pathogenic?

SFTPB p.Val63= (c.189G>A) is classified Likely benign in SFTPB (ClinVar, Single submitter, 1 submitter; last evaluated 2014-07-17). Ultra-rare (popmax 0.0117%, amr); Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with SFTPB p.Val63= (c.189G>A)?

SFTPB p.Val63= (c.189G>A) is associated with hereditary pulmonary alveolar proteinosis (ClinVar).

How common is SFTPB p.Val63= (c.189G>A) in the general population?

SFTPB p.Val63= (c.189G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

SFTPB p.Val63=

c.189G>A · rs756849429 · VCV1788595

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

hereditary pulmonary alveolar proteinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.048	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.4	GERP -3.3
Overall
CADD	3.012	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,030 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000496% 8/1,614,248 alleles · ultra-rare exomes 8/1,461,878 · genomes 0/152,370 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,576
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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: SFTPB
Protein: p.Val63=
Coding: c.189G>A
MANE Select: NM_000542
dbSNP: rs756849429
Type: single nucleotide variant
Location: chr2:85667685 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.31 · 9 PDB
Residue 63: the saposin a-type domain

Full SFTPB 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

SFTPB p.Val63Ala Likely benign ★ same residue
SFTPB p.Ala184Pro Uncertain significance ★★ ⚠ same condition
SFTPB p.Arg165Gln Uncertain significance ★★ ⚠ same condition
SFTPB p.Arg217Gln Uncertain significance ★★ ⚠ same condition
SFTPB p.Arg276Gln Uncertain significance ★★ ⚠ same condition
SFTPB p.Arg276Trp Uncertain significance ★★ ⚠ same condition
SFTPB p.Asp118Asn Uncertain significance ★★ ⚠ same condition
SFTPB p.Asp158His Uncertain significance ★★ ⚠ 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/sftpb-p-val63 (accessed [today's date]).

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