Is TRPC6 p.Ser836= (c.2508T>C) pathogenic?

TRPC6 p.Ser836= (c.2508T>C) is classified Uncertain significance in TRPC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.00237%, nfe); Associated with focal segmental glomerulosclerosis 2.

What condition is associated with TRPC6 p.Ser836= (c.2508T>C)?

TRPC6 p.Ser836= (c.2508T>C) is associated with focal segmental glomerulosclerosis 2 (ClinVar).

How common is TRPC6 p.Ser836= (c.2508T>C) in the general population?

TRPC6 p.Ser836= (c.2508T>C) is very rare (popmax 0.00237%, nfe) (gnomAD).

TRPC6 p.Ser836=

c.2508T>C · rs377172208 · VCV301900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

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 1.2	GERP -2.8, phastCons 0.9
Overall
CADD	2.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% European (non-Finnish) · 28/1,178,990 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.0018% 29/1,612,368 alleles · very rare exomes 27/1,460,214 · genomes 2/152,154 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00237%	42,107
African / African-American	0.00134%	74,812

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.Ser836=
Coding: c.2508T>C
MANE Select: NM_004621
dbSNP: rs377172208
Type: single nucleotide variant
Location: chr11:101455078 (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.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-ser836 (accessed [today's date]).

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