Is TRPM3 p.Pro36Ser (c.106C>T) pathogenic?

TRPM3 p.Pro36Ser (c.106C>T) is classified Uncertain significance in TRPM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). Very rare (popmax 0.00161%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRPM3 p.Pro36Ser (c.106C>T)?

TRPM3 p.Pro36Ser (c.106C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRPM3 p.Pro36Ser (c.106C>T) in the general population?

TRPM3 p.Pro36Ser (c.106C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

TRPM3 p.Pro36Ser

c.106C>T · rs2073592897 · VCV3183314

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.06	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.3	GERP -0.14, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 502 kb · p 1.1e-12 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,180,004 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00124% 20/1,614,134 alleles · very rare exomes 20/1,461,852 · genomes 0/152,282 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,106
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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: TRPM3
Protein: p.Pro36Ser
Coding: c.106C>T
MANE Select: NM_001366145
dbSNP: rs2073592897
Type: single nucleotide variant
Location: chr9:71121249 (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-pro36ser (accessed [today's date]).

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