Is CERKL p.Phe99fs (c.294_295del) pathogenic?

CERKL p.Phe99fs (c.294295del) is classified Pathogenic/Likely pathogenic in CERKL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-06-10). Very rare (popmax 8.49e-05%, nfe); Associated with retinitis pigmentosa 26.

What condition is associated with CERKL p.Phe99fs (c.294_295del)?

CERKL p.Phe99fs (c.294_295del) is associated with retinitis pigmentosa 26 (ClinVar).

How common is CERKL p.Phe99fs (c.294_295del) in the general population?

CERKL p.Phe99fs (c.294_295del) is very rare (popmax 8.49e-05%, 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.Phe99fs

c.294_295del · rs2468433779 · VCV2085599

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

retinitis pigmentosa 26

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 2 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,976 alleles

Overall 6.21e-05% 1/1,611,430 alleles · very rare exomes 1/1,459,120 · genomes 0/152,310 · joint denominator

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.Phe99fs
Coding: c.294_295del
MANE Select: NM_201548
dbSNP: rs2468433779
Type: Microsatellite
Location: chr2:181604023 (GRCh38)
Gene constraint: LOEUF 1.43 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82

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

Disease context

retinitis pigmentosa 26 — 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

CERKL c.1073+3_1073+6del Pathogenic/Likely pathogenic ★★ same condition
CERKL p.Cys362_Glu363delinsTer Pathogenic ★★ same condition
CERKL p.Ile150fs Pathogenic/Likely pathogenic ★★ same condition
CERKL p.Phe123fs Pathogenic/Likely pathogenic ★★ same condition
CERKL p.Glu486dup Uncertain significance ★★ same condition
CERKL p.Asp149fs Likely pathogenic ★ same condition
CERKL p.Leu213fs Likely pathogenic ★ same condition
CERKL c.613+5_613+8del 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/cerkl-p-phe99fs (accessed [today's date]).

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