Is CERKL p.Pro516= (c.1548A>C) pathogenic?

CERKL p.Pro516= (c.1548A>C) is classified Uncertain significance in CERKL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-01). Very rare (popmax 0.00447%, eas); Associated with retinitis pigmentosa.

What condition is associated with CERKL p.Pro516= (c.1548A>C)?

CERKL p.Pro516= (c.1548A>C) is associated with retinitis pigmentosa, inherited retinal dystrophy (ClinVar).

How common is CERKL p.Pro516= (c.1548A>C) in the general population?

CERKL p.Pro516= (c.1548A>C) is very rare (popmax 0.00447%, eas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

CERKL p.Pro516=

c.1548A>C · rs1687294615 · VCV895836

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.61	GERP 0.51, phastCons 0.001
Overall
CADD	8.915	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00447% East Asian · 2/44,700 alleles

Filtering AF 0.000742% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000253% 4/1,582,232 alleles · very rare exomes 3/1,430,028 · genomes 1/152,204 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,350
Remaining individualsnot grpmax-eligible	0.00163%	61,308
European (non-Finnish)	8.68e-05%	1,152,172

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.Pro516=
Coding: c.1548A>C
MANE Select: NM_201548
dbSNP: rs1687294615
Type: single nucleotide variant
Location: chr2:181538235 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited retinal dystrophy

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.1074-1G>C Pathogenic/Likely pathogenic ★★ same condition
CERKL c.1366-2A>G Likely pathogenic ★★ same condition
CERKL c.238+1G>A Pathogenic ★★ same condition
CERKL c.481+2T>G Pathogenic/Likely pathogenic ★★ same condition
CERKL c.677+547G>C Likely pathogenic ★★ same condition
CERKL c.678-1G>A Pathogenic/Likely pathogenic ★★ same condition
CERKL p.Arg106Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CERKL p.Arg106Ser Pathogenic/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-pro516 (accessed [today's date]).

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