Is TRPM1 p.Pro602Arg (c.1805C>G) pathogenic?

TRPM1 p.Pro602Arg (c.1805C>G) is classified Uncertain significance in TRPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-15). AlphaMissense: ambiguous (0.3697); Very rare (popmax 6.34e-05%); Associated with Inborn genetic diseases.

What condition is associated with TRPM1 p.Pro602Arg (c.1805C>G)?

TRPM1 p.Pro602Arg (c.1805C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TRPM1 p.Pro602Arg (c.1805C>G) in the general population?

TRPM1 p.Pro602Arg (c.1805C>G) is very rare (popmax 6.34e-05%) (gnomAD).

What do computational predictors say about TRPM1 p.Pro602Arg (c.1805C>G)?

AlphaMissense predicts ambiguous (score 0.3697) — an in-silico prediction, not a clinical call.

TRPM1 p.Pro602Arg

c.1805C>G · VCV3462072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.34e-05%)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3697	ambiguous
REVEL	0.511	indeterminate
SaProt	LLR -7.64	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP -0.59, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 53 kb · p 0.68 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P580R vs ClinVar P602R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.34e-05%

Overall 6.34e-05% 1/1,578,002 alleles · very rare exomes 1/1,425,868 · genomes 0/152,134 · 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: TRPM1
Protein: p.Pro602Arg
Coding: c.1805C>G
MANE Select: NM_001252024
Type: single nucleotide variant
Location: chr15:31042233 (GRCh38)
Gene constraint: LOEUF 0.839 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 66.74
Residue 580 UniProt numbering: the 'disordered' region

Full TRPM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRPM1 p.Ala1240Pro Uncertain significance ★★ ⚠ same condition
TRPM1 p.Ala1364Val Uncertain significance ★★ ⚠ same condition
TRPM1 p.Ala1371Pro Uncertain significance ★★ ⚠ same condition
TRPM1 p.Ala1453Asp Uncertain significance ★★ ⚠ same condition
TRPM1 p.Ala150Ser Uncertain significance ★★ ⚠ same condition
TRPM1 p.Ala1534Thr Uncertain significance ★★ ⚠ same condition
TRPM1 p.Arg1063Trp Uncertain significance ★★ ⚠ same condition
TRPM1 p.Arg1268Gln Uncertain significance ★★ ⚠ 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/trpm1-p-pro602arg (accessed [today's date]).

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