Is TRPM1 p.Val997= (c.2991C>T) pathogenic?

TRPM1 p.Val997= (c.2991C>T) is classified Benign/Likely benign in TRPM1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-06). Rare (popmax 0.839%, afr); Associated with congenital stationary night blindness 1C.

What condition is associated with TRPM1 p.Val997= (c.2991C>T)?

TRPM1 p.Val997= (c.2991C>T) is associated with congenital stationary night blindness 1C (ClinVar).

How common is TRPM1 p.Val997= (c.2991C>T) in the general population?

TRPM1 p.Val997= (c.2991C>T) is rare (popmax 0.839%, afr) (gnomAD).

TRPM1 p.Val997=

c.2991C>T · rs115529590 · VCV886331

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.839%, afr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.4	GERP -5.5
Overall
CADD	0.169	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.839% African / African-American · 630/75,046 alleles

Filtering AF 0.785% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.764%

Overall 0.0444% 716/1,614,178 alleles · rare exomes 338/1,461,892 · genomes 378/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.839%	119
Admixed American	0.0583%	1,715
Remaining individualsnot grpmax-eligible	0.0576%	1,736
Middle Eastern	0.033%	3,031
South Asian	0.00439%	22,771
European (non-Finnish)	0.000763%	131,113

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.Val997=
Coding: c.2991C>T
MANE Select: NM_001252024
dbSNP: rs115529590
Type: single nucleotide variant
Location: chr15:31031119 (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-val997 (accessed [today's date]).

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