Is TRPC7 p.Ala484Val (c.1451C>T) pathogenic?

TRPC7 p.Ala484Val (c.1451C>T) is classified Uncertain significance in TRPC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely pathogenic (0.8363); Very rare (popmax 0.00668%, eas).

How common is TRPC7 p.Ala484Val (c.1451C>T) in the general population?

TRPC7 p.Ala484Val (c.1451C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about TRPC7 p.Ala484Val (c.1451C>T)?

AlphaMissense predicts likely pathogenic (score 0.8363) — an in-silico prediction, not a clinical call.

TRPC7 p.Ala484Val

c.1451C>T · rs745537292 · VCV3183256

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8363 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8363	likely pathogenic
REVEL	0.763	pathogenic-leaning
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 105 kb · p 0.26 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 0.00668% East Asian · 3/44,892 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000186% 3/1,613,868 alleles · very rare exomes 1/1,461,686 · genomes 2/152,182 · 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: TRPC7
Protein: p.Ala484Val
Coding: c.1451C>T
MANE Select: NM_020389
dbSNP: rs745537292
Type: single nucleotide variant
Location: chr5:136251777 (GRCh38)
Gene constraint: LOEUF 0.596 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.97

Full TRPC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRPC7 p.Ala109Val Uncertain significance ★ ⚠ same type
TRPC7 p.Ala228Thr Uncertain significance ★ same type
TRPC7 p.Ala30Ser Uncertain significance ★ ⚠ same type
TRPC7 p.Ala545Thr Uncertain significance ★ ⚠ same type
TRPC7 p.Ala607Thr Uncertain significance ★ ⚠ same type
TRPC7 p.Ala737Thr Uncertain significance ★ ⚠ same type
TRPC7 p.Ala737Val Uncertain significance ★ ⚠ same type
TRPC7 p.Ala760Val Uncertain significance ★ ⚠ same type

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/trpc7-p-ala484val (accessed [today's date]).

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