Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 19.8%, afr) — too common for a highly-penetrant pathogenic allele
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 -5.2 | GERP -4.4 |
| Overall | ||
| CADD | 4.24 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
19.8%
African / African-American · 14,810/74,890 alleles
Filtering AF
19.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 19.4%
Overall
1.07%
17,321/1,613,466 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 19.8% | 5 |
| Remaining individualsnot grpmax-eligible | 1.41% | 71 |
| Middle Eastern | 1.37% | 73 |
| Admixed American | 1.3% | 77 |
| Ashkenazi Jewishnot grpmax-eligible | 0.524% | 191 |
| South Asian | 0.0637% | 1,569 |
| European (non-Finnish) | 0.0463% | 2,161 |
| Finnishnot grpmax-eligible | 0.00938% | 10,666 |
| East Asian | 0.00223% | 44,836 |
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.Ala275=
- Coding
- c.825C>T
- MANE Select
- NM_003672
- dbSNP
- rs7543221
- Type
- single nucleotide variant
- Location
- chr1:100462868 (GRCh38)
- Gene constraint
- LOEUF 1.141 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.77
- Residue 275
- the tyrosine-protein phosphatase domain; a UniProt-annotated variant site (in dfnb32); the 'b' region
Similar variants
- CDC14A p.Arg261Ter Pathogenic ★★ same type
- CDC14A p.Arg312Gln Pathogenic/Likely pathogenic ★★ same type
- CDC14A p.Arg312Gly Pathogenic/Likely pathogenic ★★ same type
- CDC14A p.Arg339Ter Pathogenic ★★ same type
- CDC14A p.Arg345Ter Pathogenic/Likely pathogenic ★★ same type
- CDC14A p.Arg376Ter Pathogenic/Likely pathogenic ★★ same type
- CDC14A p.Ala211Gly Uncertain significance ★★ ⚠ same type
- CDC14A p.Ala482Thr Uncertain significance ★★ ⚠ 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-ala275 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown