Is TRPC6 p.Ala18Pro (c.52G>C) pathogenic?

TRPC6 p.Ala18Pro (c.52G>C) is classified Uncertain significance in TRPC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0694); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRPC6 p.Ala18Pro (c.52G>C)?

TRPC6 p.Ala18Pro (c.52G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRPC6 p.Ala18Pro (c.52G>C) in the general population?

TRPC6 p.Ala18Pro (c.52G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRPC6 p.Ala18Pro (c.52G>C)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

TRPC6 p.Ala18Pro

c.52G>C · VCV4191634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -6.77	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 0.78	GERP -0.68
Regional constraint	o/e 1.42	unconstrained · MANE · 79 kb · p 8.7e-07 · regional, not allelic
Overall
CADD	12.6	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: TRPC6
Protein: p.Ala18Pro
Coding: c.52G>C
MANE Select: NM_004621
Type: single nucleotide variant
Location: chr11:101583452 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB
Residue 18: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRPC6 p.Glu897Lys Pathogenic/Likely pathogenic ★★ same condition
TRPC6 p.Ala369Asp Uncertain significance ★★ ⚠ same condition
TRPC6 p.Ala538Thr Uncertain significance ★★ ⚠ same condition
TRPC6 p.Arg73Leu Uncertain significance ★★ ⚠ same condition
TRPC6 p.Asp317Glu Uncertain significance ★★ ⚠ same condition
TRPC6 p.Gln3Arg Uncertain significance ★★ ⚠ same condition
TRPC6 p.Glu200Asp Uncertain significance ★★ ⚠ same condition
TRPC6 p.Glu797Asp Uncertain significance ★★ ⚠ 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/trpc6-p-ala18pro (accessed [today's date]).

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