Is TRPC6 p.Arg91= (c.273C>T) pathogenic?

TRPC6 p.Arg91= (c.273C>T) is classified Likely benign in TRPC6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-31). Ultra-rare (popmax 0.0168%, mid); Associated with focal segmental glomerulosclerosis 2.

What condition is associated with TRPC6 p.Arg91= (c.273C>T)?

TRPC6 p.Arg91= (c.273C>T) is associated with focal segmental glomerulosclerosis 2 (ClinVar).

How common is TRPC6 p.Arg91= (c.273C>T) in the general population?

TRPC6 p.Arg91= (c.273C>T) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

TRPC6 p.Arg91=

c.273C>T · rs140496742 · VCV2957678

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

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 0.73	GERP -1.7, phastCons 0.2
Overall
CADD	5.575	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% Middle Eastern · 1/5,952 alleles

Filtering AF 0.00229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.000689% 11/1,595,484 alleles · ultra-rare exomes 8/1,443,346 · genomes 3/152,138 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,952
Admixed American	0.00681%	14,683
Remaining individualsnot grpmax-eligible	0.00324%	30,818
European (non-Finnish)	0.000342%	292,368

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.Arg91=
Coding: c.273C>T
MANE Select: NM_004621
dbSNP: rs140496742
Type: single nucleotide variant
Location: chr11:101504696 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB

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.Arg91Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
TRPC6 p.Arg91Leu Uncertain significance ★ ⚠ same residue
TRPC6 p.Arg91His Likely benign ★ same residue
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

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-arg91 (accessed [today's date]).

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