Is TRPC1 p.Arg85Lys (c.254G>A) pathogenic?

TRPC1 p.Arg85Lys (c.254G>A) is classified Uncertain significance in TRPC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely pathogenic (0.8241); Very rare (popmax 6.2e-05%).

How common is TRPC1 p.Arg85Lys (c.254G>A) in the general population?

TRPC1 p.Arg85Lys (c.254G>A) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about TRPC1 p.Arg85Lys (c.254G>A)?

AlphaMissense predicts likely pathogenic (score 0.8241) — an in-silico prediction, not a clinical call.

TRPC1 p.Arg85Lys

c.254G>A · rs750429181 · VCV3183216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8241 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8241	likely pathogenic
REVEL	0.53	indeterminate
SaProt	LLR -10.55	damaging
⇒ AlphaMissense and SaProt both call this damaging; 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 1.24	unconstrained · MANE · 12 kb · p 0.0078 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 6.2e-05%

Overall 6.2e-05% 1/1,612,884 alleles · very rare exomes 1/1,460,616 · genomes 0/152,268 · 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: TRPC1
Protein: p.Arg85Lys
Coding: c.254G>A
MANE Select: NM_001251845
dbSNP: rs750429181
Type: single nucleotide variant
Location: chr3:142736460 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 4 PDB

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-arg85lys (accessed [today's date]).

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