Is CERKL p.Arg5= (c.15G>A) pathogenic?

CERKL p.Arg5= (c.15G>A) is classified Conflicting classifications of pathogenicity in CERKL (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-23). Rare (popmax 0.218%, amr); Associated with retinitis pigmentosa.

What condition is associated with CERKL p.Arg5= (c.15G>A)?

CERKL p.Arg5= (c.15G>A) is associated with retinitis pigmentosa, retinitis pigmentosa 26 (ClinVar).

How common is CERKL p.Arg5= (c.15G>A) in the general population?

CERKL p.Arg5= (c.15G>A) is rare (popmax 0.218%, amr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

CERKL p.Arg5=

c.15G>A · rs762405291 · VCV333016

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.218%, amr)

Conditions

retinitis pigmentosa

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 0.23	GERP 0.32, phastCons 0.14
Overall
CADD	13.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.218% Admixed American · 126/57,878 alleles

Filtering AF 0.187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.175%

Overall 0.00823% 130/1,580,358 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.218%	459
Remaining individualsnot grpmax-eligible	0.00164%	61,058
European (non-Finnish)	0.000257%	389,376

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: CERKL
Protein: p.Arg5=
Coding: c.15G>A
MANE Select: NM_201548
dbSNP: rs762405291
Type: single nucleotide variant
Location: chr2:181656992 (GRCh38)

Full CERKL 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

Also linked: retinitis pigmentosa 26

For Retinitis pigmentosa (Orphanet):

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

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/cerkl-p-arg5 (accessed [today's date]).

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