CEP170B p.Pro643Leu
c.1928C>T · VCV4226055
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0336%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.136 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP 1.5, phastCons 0.002 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 19 kb · p 0.99 · regional, not allelic |
| Overall | ||
| CADD | 12.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0336%
Middle Eastern · 2/5,954 alleles
Filtering AF
0.0168%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0139%
Overall
0.00786%
123/1,564,412 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0336% | 2,977 |
| African / African-American | 0.0257% | 3,893 |
| European (non-Finnish) | 0.00811% | 12,328 |
| Remaining individualsnot grpmax-eligible | 0.00658% | 15,202 |
| Admixed American | 0.00566% | 17,656 |
| South Asian | 0.00117% | 85,448 |
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
- CEP170B
- Protein
- p.Pro643Leu
- Coding
- c.1928C>T
- MANE Select
- NM_001112726
- Type
- single nucleotide variant
- Location
- chr14:104885526 (GRCh38)
- Gene constraint
- LOEUF 0.682 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 47.31
- Residue 643
- the 'disordered' region
Similar variants
- CEP170B p.Lys368Glu Uncertain significance ★★ same type
- CEP170B p.Pro148Leu Uncertain significance ★★ same type
- CEP170B p.Ala259Val Benign ★★ same type
- CEP170B p.Arg147= Benign ★★ same type
- CEP170B p.Ala1053Val Uncertain significance ★ same type
- CEP170B p.Ala1062Val Uncertain significance ★ same type
- CEP170B p.Ala1083Val Uncertain significance ★ same type
- CEP170B p.Ala1091Thr 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/cep170b-p-pro643leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown