Is TRPC6 p.Pro9Leu (c.26C>T) pathogenic?

TRPC6 p.Pro9Leu (c.26C>T) is classified Uncertain significance in TRPC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-28). AlphaMissense: likely benign (0.1423); No allele count reported in gnomAD v4.1 (AN 1,513,302).

How common is TRPC6 p.Pro9Leu (c.26C>T) in the general population?

TRPC6 p.Pro9Leu (c.26C>T) is no allele count reported in gnomAD v4.1 (AN 1,513,302) (gnomAD).

What do computational predictors say about TRPC6 p.Pro9Leu (c.26C>T)?

AlphaMissense predicts likely benign (score 0.1423) — an in-silico prediction, not a clinical call.

TRPC6 p.Pro9Leu

c.26C>T · VCV4913623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1423 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,513,302)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1423	likely benign
REVEL	0.336	indeterminate
SaProt	LLR -6.72	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 1.42	unconstrained · MANE · 79 kb · p 8.7e-07 · regional, not allelic
Overall
CADD	24.3	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

No allele count reported in gnomAD v4.1 (AN 1,513,302). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRPC6
Protein: p.Pro9Leu
Coding: c.26C>T
MANE Select: NM_004621
Type: single nucleotide variant
Location: chr11:101583478 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB
Residue 9: the 'disordered' region

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

Similar variants

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
TRPC6 p.Glu897Lys Pathogenic/Likely pathogenic ★★ same type
TRPC6 p.Pro112Gln 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-pro9leu (accessed [today's date]).

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