Is GNB3 p.Ser275= (c.825C>T) pathogenic?

GNB3 p.Ser275= (c.825C>T) is classified Benign in GNB3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 74.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with congenital stationary night blindness 1H.

What condition is associated with GNB3 p.Ser275= (c.825C>T)?

GNB3 p.Ser275= (c.825C>T) is associated with congenital stationary night blindness 1H (ClinVar).

GNB3 p.Ser275=

Q: How common is GNB3 p.Ser275= (c.825C>T) in the general population?

GNB3 p.Ser275= (c.825C>T) is common (popmax 74.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.825C>T · rs5443 · VCV226004

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 74.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

congenital stationary night blindness 1H

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -12	GERP -5.1
Overall
CADD	0.218	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 74.9% African / African-American · 56,185/74,964 alleles

Filtering AF 74.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 74.2%

Overall 33.7% 543,102/1,613,364 alleles · common exomes 476,344/1,461,274 · genomes 66,758/152,090 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	74.9%	1
East Asian	51.3%	2
Middle Eastern	47.3%	2
Admixed American	36.8%	3
Remaining individualsnot grpmax-eligible	36.2%	3
Amishnot grpmax-eligible	34.4%	3
South Asian	32.1%	3
Ashkenazi Jewishnot grpmax-eligible	32%	3
European (non-Finnish)	30.6%	3
Finnishnot grpmax-eligible	25.5%	4

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: GNB3
Protein: p.Ser275=
Coding: c.825C>T
MANE Select: NM_002075
dbSNP: rs5443
Type: single nucleotide variant
Location: chr12:6845711 (GRCh38)

Full GNB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

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/gnb3-p-ser275 (accessed [today's date]).

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