Is SFTPC p.Pro117= (c.351T>C) pathogenic?

SFTPC p.Pro117= (c.351T>C) is classified Benign/Likely benign in SFTPC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-16). Ultra-rare (popmax 0.0767%, amr); Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with SFTPC p.Pro117= (c.351T>C)?

SFTPC p.Pro117= (c.351T>C) is associated with hereditary pulmonary alveolar proteinosis (ClinVar).

How common is SFTPC p.Pro117= (c.351T>C) in the general population?

SFTPC p.Pro117= (c.351T>C) is ultra-rare (popmax 0.0767%, amr) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

SFTPC p.Pro117=

c.351T>C · rs35457216 · VCV1732262

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0767%, 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 -8.7	GERP -3.2
Overall
CADD	0.195	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0767% Admixed American · 46/59,994 alleles

Filtering AF 0.0591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0528%

Overall 0.00341% 55/1,613,956 alleles · ultra-rare exomes 48/1,461,734 · genomes 7/152,222 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0767%	1,304
Remaining individualsnot grpmax-eligible	0.0048%	20,828
African / African-American	0.00133%	74,942
European (non-Finnish)	0.000424%	235,999

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: SFTPC
Protein: p.Pro117=
Coding: c.351T>C
MANE Select: NM_001317778
dbSNP: rs35457216
Type: single nucleotide variant
Location: chr8:22163462 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.71 · 3 PDB
Residue 117: the brichos domain

Full SFTPC 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

SFTPC p.Pro117Thr Uncertain significance ★ ⚠ same residue
SFTPC p.Ile73Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
SFTPC p.Leu110Pro Pathogenic/Likely pathogenic ★★ same condition
SFTPC p.Ile50Met Uncertain significance ★★ ⚠ same condition
SFTPC c.43-7G>A Benign/Likely benign ★★ same condition
SFTPC c.435+12T>G Benign/Likely benign ★★ same condition
SFTPC c.435+15G>A Benign/Likely benign ★★ same condition
SFTPC c.*12T>A Benign/Likely benign ★★ 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/sftpc-p-pro117 (accessed [today's date]).

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