Is TRPC6 p.Ser552Phe (c.1655C>T) pathogenic?

TRPC6 p.Ser552Phe (c.1655C>T) is classified Uncertain significance in TRPC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.338); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRPC6 p.Ser552Phe (c.1655C>T)?

TRPC6 p.Ser552Phe (c.1655C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRPC6 p.Ser552Phe (c.1655C>T) in the general population?

TRPC6 p.Ser552Phe (c.1655C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRPC6 p.Ser552Phe (c.1655C>T)?

AlphaMissense predicts likely benign (score 0.338) — an in-silico prediction, not a clinical call.

TRPC6 p.Ser552Phe

c.1655C>T · VCV4191639

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.338 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.338	likely benign
REVEL	0.633	indeterminate
SaProt	LLR -7.92	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 28 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	29.8	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.Ser552Phe
Coding: c.1655C>T
MANE Select: NM_004621
Type: single nucleotide variant
Location: chr11:101476390 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB
Residue 552: an α-helix

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-ser552phe (accessed [today's date]).

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