Is SFTPC p.Gln145= (c.435G>A) pathogenic?

SFTPC p.Gln145= (c.435G>A) is classified Likely pathogenic in SFTPC (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-07). Absent from gnomAD v4.1; Associated with hereditary pulmonary alveolar proteinosis.

What condition is associated with SFTPC p.Gln145= (c.435G>A)?

SFTPC p.Gln145= (c.435G>A) is associated with hereditary pulmonary alveolar proteinosis (ClinVar).

How common is SFTPC p.Gln145= (c.435G>A) in the general population?

SFTPC p.Gln145= (c.435G>A) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

SFTPC p.Gln145=

c.435G>A · rs2538945951 · VCV1739999

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary pulmonary alveolar proteinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.90	donor loss · deltas
Pangolin	Δ0.72	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SFTPC
Protein: p.Gln145=
Coding: c.435G>A
MANE Select: NM_001317778
dbSNP: rs2538945951
Type: single nucleotide variant
Location: chr8:22163546 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.71 · 3 PDB
Residue 145: 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.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-gln145 (accessed [today's date]).

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