Is TRPC6 p.Leu332= (c.996C>T) pathogenic?

TRPC6 p.Leu332= (c.996C>T) is classified Benign/Likely benign in TRPC6 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-10-22). Rare (popmax 0.54%, sas); Associated with focal segmental glomerulosclerosis.

What condition is associated with TRPC6 p.Leu332= (c.996C>T)?

TRPC6 p.Leu332= (c.996C>T) is associated with focal segmental glomerulosclerosis, focal segmental glomerulosclerosis 2 (ClinVar).

How common is TRPC6 p.Leu332= (c.996C>T) in the general population?

TRPC6 p.Leu332= (c.996C>T) is rare (popmax 0.54%, sas) (gnomAD).

TRPC6 p.Leu332=

c.996C>T · rs200144852 · VCV1673701

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.54%, sas)

Conditions

focal segmental glomerulosclerosis

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 0.31	GERP 0.38, phastCons 0.94
Overall
CADD	7.595	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.54% South Asian · 492/91,068 alleles

Filtering AF 0.501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.485%

Overall 0.0321% 518/1,613,974 alleles · rare exomes 487/1,461,806 · genomes 31/152,168 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.54%	185
Remaining individualsnot grpmax-eligible	0.0368%	2,718
African / African-American	0.00133%	74,996
European (non-Finnish)	0.000169%	589,995

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.Leu332=
Coding: c.996C>T
MANE Select: NM_004621
dbSNP: rs200144852
Type: single nucleotide variant
Location: chr11:101491688 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB
Residue 332: 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-leu332 (accessed [today's date]).

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