Is TRPC6 p.Asp559= (c.1677C>T) pathogenic?

TRPC6 p.Asp559= (c.1677C>T) is classified Benign in TRPC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0495%, mid); Associated with focal segmental glomerulosclerosis 2.

What condition is associated with TRPC6 p.Asp559= (c.1677C>T)?

TRPC6 p.Asp559= (c.1677C>T) is associated with focal segmental glomerulosclerosis 2 (ClinVar).

How common is TRPC6 p.Asp559= (c.1677C>T) in the general population?

TRPC6 p.Asp559= (c.1677C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

TRPC6 p.Asp559=

c.1677C>T · rs552837414 · VCV301906

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, 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 0.17	GERP -3.8, phastCons 0.15
Overall
CADD	8.048	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,058 alleles

Filtering AF 0.0256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00626% 101/1,613,972 alleles · ultra-rare exomes 94/1,461,846 · genomes 7/152,126 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,019
South Asian	0.0351%	2,846
Remaining individualsnot grpmax-eligible	0.0112%	8,930
African / African-American	0.00934%	10,712
European (non-Finnish)	0.00415%	24,081
Admixed American	0.00333%	29,987
Finnishnot grpmax-eligible	0.00156%	63,990

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.Asp559=
Coding: c.1677C>T
MANE Select: NM_004621
dbSNP: rs552837414
Type: single nucleotide variant
Location: chr11:101476368 (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-asp559 (accessed [today's date]).

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