Is CERKL p.Pro261= (c.783T>C) pathogenic?

CERKL p.Pro261= (c.783T>C) is classified Conflicting classifications of pathogenicity in CERKL (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-28). Rare (popmax 0.558%, afr); Associated with retinitis pigmentosa.

What condition is associated with CERKL p.Pro261= (c.783T>C)?

CERKL p.Pro261= (c.783T>C) is associated with retinitis pigmentosa, retinitis pigmentosa 26 (ClinVar).

How common is CERKL p.Pro261= (c.783T>C) in the general population?

CERKL p.Pro261= (c.783T>C) is rare (popmax 0.558%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

CERKL p.Pro261=

c.783T>C · rs77741297 · VCV897708

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.558%, 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	all four deltas below 0.2 · A>C here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.7	GERP -3.9
Overall
CADD	0.281	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.558% African / African-American · 419/75,024 alleles

Filtering AF 0.514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.497%

Overall 0.0306% 494/1,613,760 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.558%	179
Middle Eastern	0.0828%	1,207
Remaining individualsnot grpmax-eligible	0.0448%	2,232
Admixed American	0.04%	2,498
South Asian	0.00439%	22,771
European (non-Finnish)	0.00119%	84,272

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.Pro261=
Coding: c.783T>C
MANE Select: NM_201548
dbSNP: rs77741297
Type: single nucleotide variant
Location: chr2:181558603 (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.Pro261fs Pathogenic ★★ same residue
CERKL p.Pro261Arg Uncertain significance ★ ⚠ same residue
CERKL c.1074-1G>C Pathogenic/Likely pathogenic ★★ same condition
CERKL c.1074-2A>C Likely pathogenic ★★ same condition
CERKL c.1074-2A>G Likely pathogenic ★★ same condition
CERKL c.1365+1G>A Likely pathogenic ★★ same condition
CERKL c.1366-1G>A Likely pathogenic ★★ same condition
CERKL c.1366-1G>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/cerkl-p-pro261 (accessed [today's date]).

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