Is TRPM1 p.Phe630= (c.1890C>T) pathogenic?

TRPM1 p.Phe630= (c.1890C>T) is classified Conflicting classifications of pathogenicity in TRPM1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-08-04). Ultra-rare (popmax 0.0119%, nfe); Associated with congenital stationary night blindness 1C.

What condition is associated with TRPM1 p.Phe630= (c.1890C>T)?

TRPM1 p.Phe630= (c.1890C>T) is associated with congenital stationary night blindness 1C (ClinVar).

How common is TRPM1 p.Phe630= (c.1890C>T) in the general population?

TRPM1 p.Phe630= (c.1890C>T) is ultra-rare (popmax 0.0119%, nfe) (gnomAD).

TRPM1 p.Phe630=

c.1890C>T · rs369315253 · VCV887382

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, nfe)

Conditions

congenital stationary night blindness 1C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -2.4, phastCons 1
Overall
CADD	11.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0119% European (non-Finnish) · 141/1,180,040 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00972%

Overall 0.00898% 145/1,614,048 alleles · ultra-rare exomes 138/1,461,882 · genomes 7/152,166 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0119%	8,369
Remaining individualsnot grpmax-eligible	0.0048%	20,830
Finnishnot grpmax-eligible	0.00156%	64,030

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.Phe630=
Coding: c.1890C>T
MANE Select: NM_001252024
dbSNP: rs369315253
Type: single nucleotide variant
Location: chr15:31042148 (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

congenital stationary night blindness 1C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRPM1 c.1089+1G>A Likely pathogenic ★★ same condition
TRPM1 c.3127+1G>A Pathogenic/Likely pathogenic ★★ same condition
TRPM1 c.3148+1G>A Pathogenic/Likely pathogenic ★★ same condition
TRPM1 c.83+1G>A Likely pathogenic ★★ same condition
TRPM1 p.Ala848Val Pathogenic/Likely pathogenic ★★ same condition
TRPM1 p.Arg646Cys Pathogenic/Likely pathogenic ★★ same condition
TRPM1 p.Arg656Ter Pathogenic/Likely pathogenic ★★ same condition
TRPM1 p.Arg899Ter Pathogenic/Likely pathogenic ★★ 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-phe630 (accessed [today's date]).

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