Is TRPC1 p.Ser16Phe (c.47C>T) pathogenic?

TRPC1 p.Ser16Phe (c.47C>T) is classified Uncertain significance in TRPC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.129); Very rare (popmax 0.00134%, afr).

How common is TRPC1 p.Ser16Phe (c.47C>T) in the general population?

TRPC1 p.Ser16Phe (c.47C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about TRPC1 p.Ser16Phe (c.47C>T)?

AlphaMissense predicts likely benign (score 0.129) — an in-silico prediction, not a clinical call.

TRPC1 p.Ser16Phe

c.47C>T · VCV4191593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.129 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.129	likely benign
REVEL	0.369	indeterminate
SaProt	LLR -9.47	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 5.7	GERP 0.65, phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 12 kb · p 0.0078 · regional, not allelic
Overall
CADD	25.1	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 0.00134% African / African-American · 1/74,618 alleles

Overall 0.000124% 2/1,608,356 alleles · very rare exomes 2/1,456,074 · genomes 0/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,618
South Asian	0.00111%	90,130

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: TRPC1
Protein: p.Ser16Phe
Coding: c.47C>T
MANE Select: NM_001251845
Type: single nucleotide variant
Location: chr3:142724606 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 4 PDB
Residue 16: the 'disordered' region

Full TRPC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRPC1 p.Ala224Val Uncertain significance ★ ⚠ same type
TRPC1 p.Ala623Thr Uncertain significance ★ ⚠ same type
TRPC1 p.Ala623Val Uncertain significance ★ ⚠ same type
TRPC1 p.Ala653Val Uncertain significance ★ ⚠ same type
TRPC1 p.Ala787Asp Uncertain significance ★ ⚠ same type
TRPC1 p.Arg169Cys Uncertain significance ★ ⚠ same type
TRPC1 p.Arg277Gln Uncertain significance ★ ⚠ same type
TRPC1 p.Arg455Cys Uncertain significance ★ ⚠ 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/trpc1-p-ser16phe (accessed [today's date]).

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