Is TRPC6 p.Pro112Ser (c.334C>T) pathogenic?

TRPC6 p.Pro112Ser (c.334C>T) is classified Uncertain significance in TRPC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely pathogenic (0.9205); Absent from gnomAD v4.1.

How common is TRPC6 p.Pro112Ser (c.334C>T) in the general population?

TRPC6 p.Pro112Ser (c.334C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRPC6 p.Pro112Ser (c.334C>T)?

AlphaMissense predicts likely pathogenic (score 0.9205) — an in-silico prediction, not a clinical call.

TRPC6 p.Pro112Ser

c.334C>T · rs2496225660 · VCV2701666

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9205 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9205	likely pathogenic
REVEL	0.533	indeterminate
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 28 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

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: TRPC6
Protein: p.Pro112Ser
Coding: c.334C>T
MANE Select: NM_004621
dbSNP: rs2496225660
Type: single nucleotide variant
Location: chr11:101504635 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB
Residue 112: a UniProt-annotated variant site (in fsgs2; increases calcium ion transport); an α-helix

Full TRPC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRPC6 p.Pro112Gln Pathogenic ★★ ⚠ same residue
TRPC6 p.Pro112= Likely benign ★ same residue
TRPC6 p.Arg175Gln Likely pathogenic ★★ ⚠ same type
TRPC6 p.Arg175Trp Pathogenic/Likely pathogenic ★★ same type
TRPC6 p.Arg895Cys Pathogenic ★★ same type
TRPC6 p.Arg895Leu Pathogenic ★★ same type
TRPC6 p.Gln869Ter Pathogenic/Likely pathogenic ★★ same type
TRPC6 p.Gln889Lys Pathogenic/Likely pathogenic ★★ ⚠ 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/trpc6-p-pro112ser (accessed [today's date]).

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