Is CNGB1 p.Pro41= (c.123G>A) pathogenic?

CNGB1 p.Pro41= (c.123G>A) is classified Conflicting classifications of pathogenicity in CNGB1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.68%, afr); Associated with retinitis pigmentosa.

What condition is associated with CNGB1 p.Pro41= (c.123G>A)?

CNGB1 p.Pro41= (c.123G>A) is associated with retinitis pigmentosa (ClinVar).

How common is CNGB1 p.Pro41= (c.123G>A) in the general population?

CNGB1 p.Pro41= (c.123G>A) is low-frequency (popmax 1.68%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CNGB1 p.Pro41=

c.123G>A · rs41482547 · VCV886364

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.68%, afr)

Conditions

retinitis pigmentosa

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 -3.5	GERP -3.6
Overall
CADD	0.205	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.68% African / African-American · 1,262/75,054 alleles

Filtering AF 1.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.57%

Overall 0.087% 1,405/1,614,192 alleles · low-frequency exomes 720/1,461,882 · genomes 685/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.68%	59
Remaining individualsnot grpmax-eligible	0.0944%	1,060
Admixed American	0.0816%	1,225
Middle Eastern	0.0165%	6,062
East Asian	0.00446%	22,440
South Asian	0.00439%	22,771
European (non-Finnish)	0.00237%	42,144

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: CNGB1
Protein: p.Pro41=
Coding: c.123G>A
MANE Select: NM_001297
dbSNP: rs41482547
Type: single nucleotide variant
Location: chr16:57967164 (GRCh38)
Gene constraint: LOEUF 0.94 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 58.89 · 11 PDB
Residue 41: the 'disordered' region

Full CNGB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CNGB1 p.Pro41Leu Uncertain significance ★★ ⚠ same residue
CNGB1 c.1957+2T>G Pathogenic ★★ same condition
CNGB1 c.1958-1G>A Pathogenic ★★ same condition
CNGB1 c.217+5G>C Pathogenic/Likely pathogenic ★★ same condition
CNGB1 c.2794+1G>A Pathogenic/Likely pathogenic ★★ same condition
CNGB1 c.2893-7G>A Pathogenic/Likely pathogenic ★★ same condition
CNGB1 c.290+2T>C Likely pathogenic ★★ same condition
CNGB1 c.412+1G>T 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/cngb1-p-pro41 (accessed [today's date]).

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