Is TRPC6 p.Pro924Ser (c.2770C>T) pathogenic?

TRPC6 p.Pro924Ser (c.2770C>T) is classified Conflicting classifications of pathogenicity in TRPC6 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-12). AlphaMissense: likely benign (0.0773); Rare (popmax 0.314%, eas); Associated with TRPC6-related disorder.

What condition is associated with TRPC6 p.Pro924Ser (c.2770C>T)?

TRPC6 p.Pro924Ser (c.2770C>T) is associated with TRPC6-related disorder, focal segmental glomerulosclerosis 2 (ClinVar).

How common is TRPC6 p.Pro924Ser (c.2770C>T) in the general population?

TRPC6 p.Pro924Ser (c.2770C>T) is rare (popmax 0.314%, eas) (gnomAD).

What do computational predictors say about TRPC6 p.Pro924Ser (c.2770C>T)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

TRPC6 p.Pro924Ser

c.2770C>T · rs139330011 · VCV301898

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.314%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TRPC6-related disorder

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -5.87	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 0.59	GERP -5.3, phastCons 0.13
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.68 · regional, not allelic
Overall
CADD	13.8	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 0.314% East Asian · 141/44,852 alleles

Filtering AF 0.272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.256%

Overall 0.0113% 182/1,613,878 alleles · rare exomes 162/1,461,596 · genomes 20/152,282 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.314%	318
Middle Eastern	0.033%	3,030
South Asian	0.0231%	4,337
Remaining individualsnot grpmax-eligible	0.0176%	5,681
European (non-Finnish)	0.000593%	168,551

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.Pro924Ser
Coding: c.2770C>T
MANE Select: NM_004621
dbSNP: rs139330011
Type: single nucleotide variant
Location: chr11:101452981 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98 · 6 PDB
Residue 924: a UniProt-annotated variant site (in fsgs2)

Full TRPC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TRPC6-related disorder

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.Gln869Ter Pathogenic/Likely 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-pro924ser (accessed [today's date]).

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