Is TRPC6 p.Phe843= (c.2529C>T) pathogenic?

TRPC6 p.Phe843= (c.2529C>T) is classified Benign in TRPC6 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Common (popmax 35.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with focal segmental glomerulosclerosis 2.

What condition is associated with TRPC6 p.Phe843= (c.2529C>T)?

TRPC6 p.Phe843= (c.2529C>T) is associated with focal segmental glomerulosclerosis 2 (ClinVar).

TRPC6 p.Phe843=

Q: How common is TRPC6 p.Phe843= (c.2529C>T) in the general population?

TRPC6 p.Phe843= (c.2529C>T) is common (popmax 35.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2529C>T · rs72984209 · VCV259460

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 35.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

focal segmental glomerulosclerosis 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.5	GERP -2.8, phastCons 1
Overall
CADD	3.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.7% African / African-American · 26,638/74,702 alleles

Filtering AF 35.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 35.2%

Overall 8.48% 136,527/1,610,434 alleles · common exomes 114,024/1,458,372 · genomes 22,503/152,062 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	35.7%	3
Middle Eastern	15.7%	6
Amishnot grpmax-eligible	10.3%	10
Remaining individualsnot grpmax-eligible	9.09%	11
Ashkenazi Jewishnot grpmax-eligible	8.1%	12
South Asian	7.93%	13
European (non-Finnish)	7.36%	14
Admixed American	6.86%	15
Finnishnot grpmax-eligible	4.38%	23
East Asian	0.0224%	4,471

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.Phe843=
Coding: c.2529C>T
MANE Select: NM_004621
dbSNP: rs72984209
Type: single nucleotide variant
Location: chr11:101455057 (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-phe843 (accessed [today's date]).

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