CERKL p.Arg4=
c.12G>A · rs765497138 · VCV2112744
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00226%, sas)
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 · C>A here scores Δ0.22 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1 | GERP -2 |
| Overall | ||
| CADD | 11.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00226%
South Asian · 2/88,666 alleles
Filtering AF
0.000374%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00014%
Overall
0.000253%
4/1,582,602 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00226% | 44,333 |
| African / African-American | 0.00135% | 73,826 |
| European (non-Finnish) | 8.55e-05% | 1,169,899 |
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.Arg4=
- Coding
- c.12G>A
- MANE Select
- NM_201548
- dbSNP
- rs765497138
- Type
- single nucleotide variant
- Location
- chr2:181656995 (GRCh38)
- Gene constraint
- LOEUF 1.43 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.82
- Residue 4
- the 'disordered' region
Similar variants
- CERKL c.1074-1G>C Pathogenic/Likely pathogenic ★★ same type
- CERKL c.1074-2A>C Likely pathogenic ★★ same type
- CERKL c.1074-2A>G Likely pathogenic ★★ same type
- CERKL c.1365+1G>A Likely pathogenic ★★ same type
- CERKL c.1366-1G>A Likely pathogenic ★★ same type
- CERKL c.1366-1G>T Likely pathogenic ★★ same type
- CERKL c.1366-2A>G Likely pathogenic ★★ same type
- CERKL c.238+1G>A Pathogenic ★★ same type
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-arg4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown