Is TRPM3 p.Ala489Ser (c.1465G>T) pathogenic?

TRPM3 p.Ala489Ser (c.1465G>T) is classified Uncertain significance in TRPM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRPM3 p.Ala489Ser (c.1465G>T)?

TRPM3 p.Ala489Ser (c.1465G>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRPM3 p.Ala489Ser (c.1465G>T) in the general population?

TRPM3 p.Ala489Ser (c.1465G>T) is absent from gnomAD v4.1 (gnomAD).

TRPM3 p.Ala489Ser

c.1465G>T · VCV3329222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.213	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 502 kb · p 1.1e-12 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

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: TRPM3
Protein: p.Ala489Ser
Coding: c.1465G>T
MANE Select: NM_001366145
Type: single nucleotide variant
Location: chr9:70639176 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 64.70 · 1 PDB

Full TRPM3 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

TRPM3 p.Arg270Gln Uncertain significance ★★ same condition
TRPM3 p.His187Arg Uncertain significance ★★ same condition
TRPM3 p.Leu504Ser Uncertain significance ★★ same condition
TRPM3 p.Lys377Thr Uncertain significance ★★ same condition
TRPM3 p.Pro827Gln Uncertain significance ★★ same condition
TRPM3 p.Ala1037Ser Uncertain significance ★ same condition
TRPM3 p.Ala1037Thr Uncertain significance ★ same condition
TRPM3 p.Ala216Val 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/trpm3-p-ala489ser (accessed [today's date]).

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