Is TRPC5 p.Arg702His (c.2105G>A) pathogenic?

TRPC5 p.Arg702His (c.2105G>A) is classified Likely benign in TRPC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-06-23). AlphaMissense: likely benign (0.2193); Rare (popmax 0.534%, afr); Associated with TRPC5-related disorder.

What condition is associated with TRPC5 p.Arg702His (c.2105G>A)?

TRPC5 p.Arg702His (c.2105G>A) is associated with TRPC5-related disorder (ClinVar).

How common is TRPC5 p.Arg702His (c.2105G>A) in the general population?

TRPC5 p.Arg702His (c.2105G>A) is rare (popmax 0.534%, afr) (gnomAD).

What do computational predictors say about TRPC5 p.Arg702His (c.2105G>A)?

AlphaMissense predicts likely benign (score 0.2193) — an in-silico prediction, not a clinical call.

TRPC5 p.Arg702His

c.2105G>A · rs36047478 · VCV3051317

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2193 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.534%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

TRPC5-related disorder

Computational evidence

Protein change
AlphaMissense	0.2193	likely benign
REVEL	0.439	indeterminate
SaProt	LLR -8.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 5,681 bp · p 0.061 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.534% African / African-American · 304/56,934 alleles

Filtering AF 0.485% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.465%

Overall 0.03% 362/1,206,627 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.534%	187
Remaining individualsnot grpmax-eligible	0.04%	2,499
Admixed American	0.0219%	4,571
Ashkenazi Jewishnot grpmax-eligible	0.0136%	7,336
East Asian	0.0119%	8,420
South Asian	0.00529%	18,894
European (non-Finnish)	0.00213%	46,980

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.Arg702His
Coding: c.2105G>A
MANE Select: NM_012471
dbSNP: rs36047478
Type: single nucleotide variant
Location: chrX:111781202 (GRCh38)
Structure: AlphaFold pLDDT 73.82 · 30 PDB
Residue 702: a UniProt-annotated variant site (in)

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

Disease context

TRPC5-related disorder

Similar variants

TRPC5 p.Arg222Cys Uncertain significance ★ ⚠ same condition
TRPC5 p.Gln914Glu Uncertain significance ★ ⚠ same condition
TRPC5 p.Lys7Gln Uncertain significance ★ ⚠ same condition
TRPC5 p.Ala912Thr Uncertain significance ⚠ same condition
TRPC5 p.Arg120Trp Uncertain significance ⚠ same condition
TRPC5 p.Arg191His Uncertain significance ⚠ same condition
TRPC5 p.Arg260Trp Uncertain significance ⚠ same condition
TRPC5 p.Arg324Gln 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/trpc5-p-arg702his (accessed [today's date]).

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