Is TRPC6 p.Gly830Arg (c.2488G>A) pathogenic?

TRPC6 p.Gly830Arg (c.2488G>A) is classified Conflicting classifications of pathogenicity in TRPC6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-06-12). AlphaMissense: likely benign (0.0906); Ultra-rare (popmax 0.066%, mid); Associated with kidney disorder.

What condition is associated with TRPC6 p.Gly830Arg (c.2488G>A)?

TRPC6 p.Gly830Arg (c.2488G>A) is associated with kidney disorder, focal segmental glomerulosclerosis 2 (ClinVar).

How common is TRPC6 p.Gly830Arg (c.2488G>A) in the general population?

TRPC6 p.Gly830Arg (c.2488G>A) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about TRPC6 p.Gly830Arg (c.2488G>A)?

AlphaMissense predicts likely benign (score 0.0906) — an in-silico prediction, not a clinical call.

TRPC6 p.Gly830Arg

c.2488G>A · rs199810047 · VCV1712370

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0906 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

kidney disorder

Computational evidence

Protein change
AlphaMissense	0.0906	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP 0.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.68 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,064 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00155% 25/1,611,102 alleles · ultra-rare exomes 21/1,459,068 · genomes 4/152,034 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
Admixed American	0.00668%	14,976
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,526
Remaining individualsnot grpmax-eligible	0.00321%	31,152
European (non-Finnish)	0.00119%	84,148

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.Gly830Arg
Coding: c.2488G>A
MANE Select: NM_004621
dbSNP: rs199810047
Type: single nucleotide variant
Location: chr11:101455098 (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

kidney disorder — 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-gly830arg (accessed [today's date]).

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