Is TRPC6 p.Arg25= (c.75C>T) pathogenic?

TRPC6 p.Arg25= (c.75C>T) is classified Conflicting classifications of pathogenicity in TRPC6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-24). Ultra-rare (popmax 0.0647%, afr); Associated with focal segmental glomerulosclerosis 2.

What condition is associated with TRPC6 p.Arg25= (c.75C>T)?

TRPC6 p.Arg25= (c.75C>T) is associated with focal segmental glomerulosclerosis 2 (ClinVar).

How common is TRPC6 p.Arg25= (c.75C>T) in the general population?

TRPC6 p.Arg25= (c.75C>T) is ultra-rare (popmax 0.0647%, afr) (gnomAD).

TRPC6 p.Arg25=

c.75C>T · rs201051533 · VCV749308

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0647%, afr)

Conditions

focal segmental glomerulosclerosis 2

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 5.6	GERP 1.3, phastCons 1
Overall
CADD	15.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0647% African / African-American · 47/72,670 alleles

Filtering AF 0.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0448%

Overall 0.00424% 66/1,554,938 alleles · ultra-rare exomes 37/1,402,580 · genomes 29/152,358 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0647%	1,546
Middle Eastern	0.0337%	2,970
Admixed American	0.00559%	17,875
Remaining individualsnot grpmax-eligible	0.00333%	30,062
European (non-Finnish)	0.00104%	95,807

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: TRPC6
Protein: p.Arg25=
Coding: c.75C>T
MANE Select: NM_004621
dbSNP: rs201051533
Type: single nucleotide variant
Location: chr11:101583429 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB
Residue 25: the 'disordered' region

Full TRPC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

focal segmental glomerulosclerosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRPC6 p.Arg175Gln Likely pathogenic ★★ ⚠ same condition
TRPC6 p.Arg175Trp Pathogenic/Likely pathogenic ★★ same condition
TRPC6 p.Arg895Cys Pathogenic ★★ same condition
TRPC6 p.Arg895Leu Pathogenic ★★ same condition
TRPC6 p.Gln889Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
TRPC6 p.Glu897Lys Pathogenic/Likely pathogenic ★★ same condition
TRPC6 p.Pro112Gln Pathogenic ★★ ⚠ same condition
TRPC6 c.170+5G>C 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/trpc6-p-arg25 (accessed [today's date]).

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