CDC14A p.Ile259=
c.777C>T · VCV3353179
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0223%, eas)
Conditions
1
CDC14A-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.68 | GERP 0.48, phastCons 0.008 |
| Overall | ||
| CADD | 15.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0223%
East Asian · 10/44,876 alleles
Filtering AF
0.012%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00917%
Overall
0.0013%
21/1,613,942 alleles · ultra-rare
exomes 20/1,461,838 · genomes 1/152,104 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0223% | 4,488 |
| South Asian | 0.0022% | 45,537 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| European (non-Finnish) | 0.000678% | 147,502 |
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
- CDC14A
- Protein
- p.Ile259=
- Coding
- c.777C>T
- MANE Select
- NM_003672
- Type
- single nucleotide variant
- Location
- chr1:100462820 (GRCh38)
- Gene constraint
- LOEUF 1.141 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.77
- Residue 259
- the tyrosine-protein phosphatase domain; a UniProt-annotated variant site (in dfnb32); the 'b' region
Disease context
CDC14A-related disorder
Similar variants
- CDC14A c.839-3C>G Likely pathogenic ★ same condition
- CDC14A c.1755+5584C>G Likely benign same condition
- CDC14A c.49+10A>T Likely benign same condition
- CDC14A p.Tyr297= Likely benign same condition
- CDC14A p.Ala3fs Likely pathogenic ★ same condition
- CDC14A p.Arg261Ter Pathogenic ★★ same type
- CDC14A p.Arg312Gln Pathogenic/Likely pathogenic ★★ same type
- CDC14A p.Arg312Gly Pathogenic/Likely 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/cdc14a-p-ile259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown