Is TRPC6 p.Ser893Ile (c.2678G>T) pathogenic?

TRPC6 p.Ser893Ile (c.2678G>T) is classified Conflicting classifications of pathogenicity in TRPC6 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-28). AlphaMissense: likely pathogenic (0.9872); Absent from gnomAD v4.1; Associated with focal segmental glomerulosclerosis 2.

What condition is associated with TRPC6 p.Ser893Ile (c.2678G>T)?

TRPC6 p.Ser893Ile (c.2678G>T) is associated with focal segmental glomerulosclerosis 2 (ClinVar).

How common is TRPC6 p.Ser893Ile (c.2678G>T) in the general population?

TRPC6 p.Ser893Ile (c.2678G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRPC6 p.Ser893Ile (c.2678G>T)?

AlphaMissense predicts likely pathogenic (score 0.9872) — an in-silico prediction, not a clinical call.

TRPC6 p.Ser893Ile

c.2678G>T · rs1591517921 · VCV805688

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 2

Computational evidence

Protein change
AlphaMissense	0.9872	likely pathogenic
REVEL	0.811	moderately pathogenic-leaning
SaProt	LLR -13.82	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.68 · regional, not allelic
Overall
CADD	30.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRPC6
Protein: p.Ser893Ile
Coding: c.2678G>T
MANE Select: NM_004621
dbSNP: rs1591517921
Type: single nucleotide variant
Location: chr11:101453073 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB
Residue 893: an α-helix; a UniProt-annotated variant site (in fsgs2)

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.Ser893Thr 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-ser893ile (accessed [today's date]).

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