Is TRPC6 p.Phe102Ile (c.304T>A) pathogenic?

TRPC6 p.Phe102Ile (c.304T>A) is classified Uncertain significance in TRPC6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely pathogenic (0.9576); Very rare (popmax 0.00111%, nfe); Associated with focal segmental glomerulosclerosis 2.

What condition is associated with TRPC6 p.Phe102Ile (c.304T>A)?

TRPC6 p.Phe102Ile (c.304T>A) is associated with focal segmental glomerulosclerosis 2 (ClinVar).

How common is TRPC6 p.Phe102Ile (c.304T>A) in the general population?

TRPC6 p.Phe102Ile (c.304T>A) is very rare (popmax 0.00111%, nfe) (gnomAD).

What do computational predictors say about TRPC6 p.Phe102Ile (c.304T>A)?

AlphaMissense predicts likely pathogenic (score 0.9576) — an in-silico prediction, not a clinical call.

TRPC6 p.Phe102Ile

c.304T>A · rs201363468 · VCV266010

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9576 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 2

Computational evidence

Protein change
AlphaMissense	0.9576	likely pathogenic
REVEL	0.925	moderately pathogenic-leaning
SaProt	LLR -14.54	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 11	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 28 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00111% European (non-Finnish) · 13/1,174,396 alleles

Filtering AF 0.000618% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000476%

Overall 0.00081% 13/1,604,974 alleles · very rare exomes 11/1,452,782 · genomes 2/152,192 · joint denominator

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.Phe102Ile
Coding: c.304T>A
MANE Select: NM_004621
dbSNP: rs201363468
Type: single nucleotide variant
Location: chr11:101504665 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB
Residue 102: 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.Phe102Leu 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-phe102ile (accessed [today's date]).

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