Is CERKL p.Pro261fs (c.780del) pathogenic?

CERKL p.Pro261fs (c.780del) is classified Pathogenic in CERKL (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-07-07). Very rare (popmax 0.00653%, nfe); Associated with retinitis pigmentosa.

What condition is associated with CERKL p.Pro261fs (c.780del)?

CERKL p.Pro261fs (c.780del) is associated with retinitis pigmentosa, retinitis pigmentosa 26 (ClinVar).

How common is CERKL p.Pro261fs (c.780del) in the general population?

CERKL p.Pro261fs (c.780del) is very rare (popmax 0.00653%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

CERKL p.Pro261fs

c.780del · rs398122964 · VCV91394

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00653%, nfe)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00653% European (non-Finnish) · 77/1,179,832 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00483% 78/1,613,616 alleles · very rare exomes 76/1,461,506 · genomes 2/152,110 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00653%	15,323
African / African-American	0.00134%	74,888

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.Pro261fs
Coding: c.780del
MANE Select: NM_201548
dbSNP: rs398122964
Type: Deletion
Location: chr2:181558606 (GRCh38)
Gene constraint: LOEUF 1.43 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82
Residue 261: the dagkc domain

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)

Similar variants

CERKL p.Pro261= Conflicting classifications of pathogenicity ★ same residue
CERKL c.1133+2del Likely pathogenic ★★ same condition
CERKL c.237_238+13del Pathogenic/Likely pathogenic ★★ same condition
CERKL c.677+562del Pathogenic/Likely pathogenic ★★ same condition
CERKL p.Asn142fs Pathogenic/Likely pathogenic ★★ same condition
CERKL p.Cys107_Ser108insTer Pathogenic/Likely pathogenic ★★ same condition
CERKL p.Gln74fs Pathogenic/Likely pathogenic ★★ same condition
CERKL p.Glu218fs 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/cerkl-p-pro261fs (accessed [today's date]).

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