Is GRM6 p.Val243Phe (c.727G>T) pathogenic?

GRM6 p.Val243Phe (c.727G>T) is classified Benign/Likely benign in GRM6 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-26). AlphaMissense: ambiguous (0.3499); Low-frequency (popmax 1.4%, mid); Associated with congenital stationary night blindness 1B.

What condition is associated with GRM6 p.Val243Phe (c.727G>T)?

GRM6 p.Val243Phe (c.727G>T) is associated with congenital stationary night blindness 1B (ClinVar).

How common is GRM6 p.Val243Phe (c.727G>T) in the general population?

GRM6 p.Val243Phe (c.727G>T) is low-frequency (popmax 1.4%, mid) (gnomAD).

What do computational predictors say about GRM6 p.Val243Phe (c.727G>T)?

AlphaMissense predicts ambiguous (score 0.3499) — an in-silico prediction, not a clinical call.

GRM6 p.Val243Phe

c.727G>T · rs17078894 · VCV99657

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

ambiguous

0.3499 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.4%, mid)

Conditions

congenital stationary night blindness 1B

Computational evidence

Protein change
AlphaMissense	0.3499	ambiguous
REVEL	0.604	indeterminate
SaProt	LLR -11.61	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 2.1, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 13 kb · p 0.88 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.4% Middle Eastern · 85/6,058 alleles

Filtering AF 1.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.26%

Overall 0.37% 5,974/1,612,786 alleles · low-frequency exomes 5,492/1,460,716 · genomes 482/152,070 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	3.82%	26
Middle Easterngrpmax	1.4%	71
South Asian	1.35%	74
Remaining individualsnot grpmax-eligible	0.563%	177
European (non-Finnish)	0.254%	393
Admixed American	0.195%	513
African / African-American	0.0454%	2,204
Finnishnot grpmax-eligible	0.036%	2,781
East Asian	0.00446%	22,415

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: GRM6
Protein: p.Val243Phe
Coding: c.727G>T
MANE Select: NM_000843
dbSNP: rs17078894
Type: single nucleotide variant
Location: chr5:178991554 (GRCh38)
Gene constraint: LOEUF 1.229 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 5 PDB

Full GRM6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

GRM6 p.Val243Leu Uncertain significance ★ ⚠ same residue
GRM6 p.Arg446Ter Pathogenic ★★ same condition
GRM6 p.Arg621Ter Pathogenic ★★ same condition
GRM6 p.Gln708Ter Pathogenic ★★ same condition
GRM6 p.Pro46Leu Likely pathogenic ★★ same condition
GRM6 p.Ala175Gly Uncertain significance ★★ same condition
GRM6 p.Arg677His Uncertain significance ★★ ⚠ same condition
GRM6 p.Cys522Tyr 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/grm6-p-val243phe (accessed [today's date]).

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