Is TRPM7 p.Gly826Val (c.2477G>T) pathogenic?

TRPM7 p.Gly826Val (c.2477G>T) is classified Uncertain significance in TRPM7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.0761); Ultra-rare (popmax 0.0322%, afr).

How common is TRPM7 p.Gly826Val (c.2477G>T) in the general population?

TRPM7 p.Gly826Val (c.2477G>T) is ultra-rare (popmax 0.0322%, afr) (gnomAD).

What do computational predictors say about TRPM7 p.Gly826Val (c.2477G>T)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

TRPM7 p.Gly826Val

c.2477G>T · VCV4191838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0322%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -6.01	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 2.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 4,987 bp · p 0.026 · regional, not allelic
Overall
CADD	17.02	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0322% African / African-American · 24/74,448 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00149% 24/1,606,492 alleles · ultra-rare exomes 6/1,454,626 · genomes 18/151,866 · 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: TRPM7
Protein: p.Gly826Val
Coding: c.2477G>T
MANE Select: NM_017672
Type: single nucleotide variant
Location: chr15:50609684 (GRCh38)
Gene constraint: LOEUF 0.681 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.90

Full TRPM7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRPM7 p.Arg197Gln Uncertain significance ★★ ⚠ same type
TRPM7 p.Gln1523Arg Uncertain significance ★★ ⚠ same type
TRPM7 p.His1443Tyr Uncertain significance ★★ ⚠ same type
TRPM7 p.His1643Arg Uncertain significance ★★ ⚠ same type
TRPM7 p.Lys714Thr Uncertain significance ★★ ⚠ same type
TRPM7 p.Pro1841His Uncertain significance ★★ ⚠ same type
TRPM7 p.Thr269Ser Uncertain significance ★★ ⚠ same type
TRPM7 p.Thr842Met 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/trpm7-p-gly826val (accessed [today's date]).

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