Is SFTPC p.His32Arg (c.95A>G) pathogenic?

SFTPC p.His32Arg (c.95A>G) is classified Uncertain significance in SFTPC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-26). AlphaMissense: likely benign (0.1479); Absent from gnomAD v4.1.

How common is SFTPC p.His32Arg (c.95A>G) in the general population?

SFTPC p.His32Arg (c.95A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SFTPC p.His32Arg (c.95A>G)?

AlphaMissense predicts likely benign (score 0.1479) — an in-silico prediction, not a clinical call.

SFTPC p.His32Arg

c.95A>G · VCV3678900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1479 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1479	likely benign
REVEL	0.226	benign-leaning
SaProt	LLR -5.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.28, phastCons 0.006
Regional constraint	o/e 0.87	unconstrained · MANE · 2,209 bp · p 0.036 · regional, not allelic
Overall
CADD	10.42	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.His32Arg
Coding: c.95A>G
MANE Select: NM_001317778
Type: single nucleotide variant
Location: chr8:22162626 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.71 · 3 PDB

Full SFTPC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SFTPC p.His32Leu Uncertain significance ★ ⚠ same residue
SFTPC p.His32Pro Uncertain significance ★ ⚠ same residue
SFTPC p.His32Tyr Benign ★ same residue
SFTPC c.435+2T>C Pathogenic/Likely pathogenic ★★ same type
SFTPC p.Ile73Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
SFTPC p.Leu110Pro Pathogenic/Likely pathogenic ★★ same type
SFTPC p.Leu55Phe Likely pathogenic ★★ ⚠ same type
SFTPC c.*193C>A Uncertain significance ★★ same type

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-his32arg (accessed [today's date]).

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