Is TRPC5 p.Arg791= (c.2371C>A) pathogenic?

TRPC5 p.Arg791= (c.2371C>A) is classified Likely benign in TRPC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-10-29). Ultra-rare (popmax 0.0271%, nfe); Associated with TRPC5-related disorder.

What condition is associated with TRPC5 p.Arg791= (c.2371C>A)?

TRPC5 p.Arg791= (c.2371C>A) is associated with TRPC5-related disorder (ClinVar).

How common is TRPC5 p.Arg791= (c.2371C>A) in the general population?

TRPC5 p.Arg791= (c.2371C>A) is ultra-rare (popmax 0.0271%, nfe) (gnomAD).

TRPC5 p.Arg791=

c.2371C>A · rs138566611 · VCV3029850

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0271%, nfe)

Conditions

TRPC5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 2.2, phastCons 1
Overall
CADD	9.361	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0271% European (non-Finnish) · 243/895,191 alleles

Filtering AF 0.0243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0232%

Overall 0.0205% 248/1,209,741 alleles · ultra-rare exomes 241/1,097,931 · genomes 7/111,810 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0271%	3,684
African / African-American	0.007%	14,291
Remaining individualsnot grpmax-eligible	0.0021%	47,582

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.Arg791=
Coding: c.2371C>A
MANE Select: NM_012471
dbSNP: rs138566611
Type: single nucleotide variant
Location: chrX:111776864 (GRCh38)
Structure: AlphaFold pLDDT 73.82 · 30 PDB
Residue 791: the 'disordered' region

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

Disease context

TRPC5-related disorder

Similar variants

TRPC5 p.Arg791Trp Uncertain significance ★ ⚠ same residue
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

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-arg791 (accessed [today's date]).

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