Is SFTPC p.Pro172= (c.516G>A) pathogenic?

SFTPC p.Pro172= (c.516G>A) is classified Likely benign in SFTPC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-27). Ultra-rare (popmax 0.0533%, afr); Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with SFTPC p.Pro172= (c.516G>A)?

SFTPC p.Pro172= (c.516G>A) is associated with hereditary pulmonary alveolar proteinosis (ClinVar).

How common is SFTPC p.Pro172= (c.516G>A) in the general population?

SFTPC p.Pro172= (c.516G>A) is ultra-rare (popmax 0.0533%, afr) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

SFTPC p.Pro172=

c.516G>A · rs149606090 · VCV1746994

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, 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 1.7	GERP -1.1, phastCons 0.94
Overall
CADD	7.254	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0533% African / African-American · 40/75,026 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0356%

Overall 0.0036% 58/1,612,732 alleles · ultra-rare exomes 34/1,460,360 · genomes 24/152,372 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0533%	1,876
Middle Eastern	0.0194%	5,144
Remaining individualsnot grpmax-eligible	0.0128%	7,799
Admixed American	0.00999%	10,006
South Asian	0.0022%	45,514
European (non-Finnish)	8.47e-05%	1,180,026

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.Pro172=
Coding: c.516G>A
MANE Select: NM_001317778
dbSNP: rs149606090
Type: single nucleotide variant
Location: chr8:22163981 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.71 · 3 PDB
Residue 172: the brichos domain; a β-strand

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.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
SFTPC p.Arg23Gln 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-pro172 (accessed [today's date]).

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