Is TRPC6 p.Val829Asp (c.2486T>A) pathogenic?

TRPC6 p.Val829Asp (c.2486T>A) is classified Uncertain significance in TRPC6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-10-25). AlphaMissense: likely benign (0.0813); Ultra-rare (popmax 0.0166%, mid); Associated with focal segmental glomerulosclerosis 2.

What condition is associated with TRPC6 p.Val829Asp (c.2486T>A)?

TRPC6 p.Val829Asp (c.2486T>A) is associated with focal segmental glomerulosclerosis 2 (ClinVar).

How common is TRPC6 p.Val829Asp (c.2486T>A) in the general population?

TRPC6 p.Val829Asp (c.2486T>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about TRPC6 p.Val829Asp (c.2486T>A)?

AlphaMissense predicts likely benign (score 0.0813) — an in-silico prediction, not a clinical call.

TRPC6 p.Val829Asp

c.2486T>A · rs1858853619 · VCV1028795

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0813 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 2

Computational evidence

Protein change
AlphaMissense	0.0813	likely benign
REVEL	0.232	benign-leaning
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -1.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.68 · regional, not allelic
Overall
CADD	16.51	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,040 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,611,344 alleles · ultra-rare exomes 4/1,459,086 · genomes 0/152,258 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,040
Remaining individualsnot grpmax-eligible	0.0016%	62,332
European (non-Finnish)	0.00017%	589,039

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.Val829Asp
Coding: c.2486T>A
MANE Select: NM_004621
dbSNP: rs1858853619
Type: single nucleotide variant
Location: chr11:101455100 (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-val829asp (accessed [today's date]).

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