Is TRPC5 p.Arg263Lys (c.788G>A) pathogenic?

TRPC5 p.Arg263Lys (c.788G>A) is classified Uncertain significance in TRPC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-22). AlphaMissense: likely benign (0.113); Ultra-rare (popmax 0.0527%, afr).

How common is TRPC5 p.Arg263Lys (c.788G>A) in the general population?

TRPC5 p.Arg263Lys (c.788G>A) is ultra-rare (popmax 0.0527%, afr) (gnomAD).

What do computational predictors say about TRPC5 p.Arg263Lys (c.788G>A)?

AlphaMissense predicts likely benign (score 0.113) — an in-silico prediction, not a clinical call.

TRPC5 p.Arg263Lys

c.788G>A · rs140314400 · VCV2216393

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.113 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.113	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 131 kb · p 1e-26 · regional, not allelic
Overall
CADD	23.3	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

Grpmax group 0.0527% African / African-American · 30/56,971 alleles

Filtering AF 0.0378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0328%

Overall 0.00256% 31/1,209,616 alleles · ultra-rare exomes 16/1,098,240 · genomes 15/111,376 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0527%	1,899
Remaining individualsnot grpmax-eligible	0.0021%	47,587

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: TRPC5
Protein: p.Arg263Lys
Coding: c.788G>A
MANE Select: NM_012471
dbSNP: rs140314400
Type: single nucleotide variant
Location: chrX:111912403 (GRCh38)
Structure: AlphaFold pLDDT 73.82 · 30 PDB
Residue 263: an α-helix

Full TRPC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRPC5 p.Ala929Thr Uncertain significance ★ ⚠ same type
TRPC5 p.Arg120Gln Uncertain significance ★ ⚠ same type
TRPC5 p.Arg175Cys Uncertain significance ★ ⚠ same type
TRPC5 p.Arg17Cys Uncertain significance ★ ⚠ same type
TRPC5 p.Arg17His Uncertain significance ★ ⚠ same type
TRPC5 p.Arg17Leu Uncertain significance ★ ⚠ same type
TRPC5 p.Arg222Cys Uncertain significance ★ ⚠ same type
TRPC5 p.Arg464Cys 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/trpc5-p-arg263lys (accessed [today's date]).

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