Is TRPC6 p.Pro55Ser (c.163C>T) pathogenic?

TRPC6 p.Pro55Ser (c.163C>T) is classified Uncertain significance in TRPC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: likely benign (0.0828); Very rare (popmax 0.000599%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRPC6 p.Pro55Ser (c.163C>T)?

TRPC6 p.Pro55Ser (c.163C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRPC6 p.Pro55Ser (c.163C>T) in the general population?

TRPC6 p.Pro55Ser (c.163C>T) is very rare (popmax 0.000599%, nfe) (gnomAD).

What do computational predictors say about TRPC6 p.Pro55Ser (c.163C>T)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

TRPC6 p.Pro55Ser

c.163C>T · rs1357621513 · VCV2605109

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000599%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign
REVEL	0.442	indeterminate
SaProt	LLR -5.75	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 5.1	GERP 0.54, phastCons 1
Regional constraint	o/e 1.42	unconstrained · MANE · 79 kb · p 8.7e-07 · regional, not allelic
Overall
CADD	19.32	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

Grpmax group 0.000599% European (non-Finnish) · 7/1,168,398 alleles

Filtering AF 0.000249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00016%

Overall 0.000441% 7/1,588,998 alleles · very rare exomes 6/1,436,758 · genomes 1/152,240 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TRPC6
Protein: p.Pro55Ser
Coding: c.163C>T
MANE Select: NM_004621
dbSNP: rs1357621513
Type: single nucleotide variant
Location: chr11:101583341 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB

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.Pro55Thr Uncertain significance ★ ⚠ same residue
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

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-pro55ser (accessed [today's date]).

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