Is GRM6 p.His511= (c.1533C>T) pathogenic?

GRM6 p.His511= (c.1533C>T) is classified Benign/Likely benign in GRM6 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.28%, afr); Associated with congenital stationary night blindness 1B.

What condition is associated with GRM6 p.His511= (c.1533C>T)?

GRM6 p.His511= (c.1533C>T) is associated with congenital stationary night blindness 1B (ClinVar).

How common is GRM6 p.His511= (c.1533C>T) in the general population?

GRM6 p.His511= (c.1533C>T) is low-frequency (popmax 1.28%, afr) (gnomAD).

GRM6 p.His511=

c.1533C>T · rs61733043 · VCV522285

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.28%, afr)

Conditions

congenital stationary night blindness 1B

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 -2.7	GERP -4.2
Overall
CADD	3.248	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.28% African / African-American · 960/75,042 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.19%

Overall 0.293% 4,704/1,605,144 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.28%	78
European (non-Finnish)	0.281%	356
Remaining individualsnot grpmax-eligible	0.28%	357
Finnishnot grpmax-eligible	0.228%	438
Admixed American	0.17%	588
South Asian	0.0231%	4,336
Middle Eastern	0.0165%	6,060
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,857
East Asian	0.00669%	14,941

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.His511=
Coding: c.1533C>T
MANE Select: NM_000843
dbSNP: rs61733043
Type: single nucleotide variant
Location: chr5:178986721 (GRCh38)
Gene constraint: LOEUF 1.229 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 5 PDB
Residue 511: a disulfide bond

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.His511Arg Benign/Likely benign ★★ 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-his511 (accessed [today's date]).

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