Is TRPC6 p.Tyr705= (c.2115C>T) pathogenic?

TRPC6 p.Tyr705= (c.2115C>T) is classified Benign/Likely benign in TRPC6 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-01). Common (popmax 10.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with focal segmental glomerulosclerosis.

What condition is associated with TRPC6 p.Tyr705= (c.2115C>T)?

TRPC6 p.Tyr705= (c.2115C>T) is associated with focal segmental glomerulosclerosis, focal segmental glomerulosclerosis 2 (ClinVar).

TRPC6 p.Tyr705=

Q: How common is TRPC6 p.Tyr705= (c.2115C>T) in the general population?

TRPC6 p.Tyr705= (c.2115C>T) is common (popmax 10.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2115C>T · rs61743044 · VCV259458

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 10.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

focal segmental glomerulosclerosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.047	GERP -4.1, phastCons 0.039
Overall
CADD	2.371	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.5% African / African-American · 7,877/74,938 alleles

Filtering AF 10.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.2%

Overall 2.35% 37,880/1,612,978 alleles · common exomes 31,622/1,460,798 · genomes 6,258/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.5%	10
Middle Eastern	2.82%	35
Remaining individualsnot grpmax-eligible	2.54%	39
Ashkenazi Jewishnot grpmax-eligible	2.49%	40
European (non-Finnish)	2.17%	46
Admixed American	1.26%	79
Finnishnot grpmax-eligible	0.814%	123
South Asian	0.689%	145
Amishnot grpmax-eligible	0.11%	912
East Asian	0.00669%	14,947

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.Tyr705=
Coding: c.2115C>T
MANE Select: NM_004621
dbSNP: rs61743044
Type: single nucleotide variant
Location: chr11:101472227 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB
Residue 705: an α-helix

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

Disease context

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

Also linked: focal segmental glomerulosclerosis 2

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-tyr705 (accessed [today's date]).

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