Is TRPC6 p.Asp633= (c.1899C>T) pathogenic?

TRPC6 p.Asp633= (c.1899C>T) is classified Likely benign in TRPC6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-05). Ultra-rare (popmax 0.033%, mid); Associated with focal segmental glomerulosclerosis 2.

What condition is associated with TRPC6 p.Asp633= (c.1899C>T)?

TRPC6 p.Asp633= (c.1899C>T) is associated with focal segmental glomerulosclerosis 2 (ClinVar).

How common is TRPC6 p.Asp633= (c.1899C>T) in the general population?

TRPC6 p.Asp633= (c.1899C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

TRPC6 p.Asp633=

c.1899C>T · rs187196477 · VCV878482

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, 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 0.74	GERP -2.1, phastCons 0.99
Overall
CADD	4.563	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,052 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.0075% 121/1,613,798 alleles · ultra-rare exomes 108/1,461,524 · genomes 13/152,274 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,026
Admixed American	0.02%	5,000
Remaining individualsnot grpmax-eligible	0.016%	6,249
European (non-Finnish)	0.00814%	12,289
South Asian	0.0011%	91,080

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.Asp633=
Coding: c.1899C>T
MANE Select: NM_004621
dbSNP: rs187196477
Type: single nucleotide variant
Location: chr11:101473619 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB
Residue 633: an α-helix

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.Asp633His Uncertain significance ★ ⚠ 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
TRPC6 p.Glu897Lys Pathogenic/Likely pathogenic ★★ same condition
TRPC6 p.Pro112Gln 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-asp633 (accessed [today's date]).

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