Is TRPM1 p.Pro1069Ser (c.3205C>T) pathogenic?

TRPM1 p.Pro1069Ser (c.3205C>T) is classified Uncertain significance in TRPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely pathogenic (0.5936); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRPM1 p.Pro1069Ser (c.3205C>T)?

TRPM1 p.Pro1069Ser (c.3205C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRPM1 p.Pro1069Ser (c.3205C>T) in the general population?

TRPM1 p.Pro1069Ser (c.3205C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRPM1 p.Pro1069Ser (c.3205C>T)?

AlphaMissense predicts likely pathogenic (score 0.5936) — an in-silico prediction, not a clinical call.

TRPM1 p.Pro1069Ser

c.3205C>T · VCV4633707

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5936 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5936	likely pathogenic
REVEL	0.594	indeterminate
SaProt	LLR -9.42	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 1,473 bp · p 0.00013 · regional, not allelic
Overall
CADD	25.3	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 P1047S vs ClinVar P1069S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRPM1
Protein: p.Pro1069Ser
Coding: c.3205C>T
MANE Select: NM_001252024
Type: single nucleotide variant
Location: chr15:31028420 (GRCh38)
Gene constraint: LOEUF 0.839 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 66.74

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-pro1069ser (accessed [today's date]).

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