CDC5L p.Leu721=
c.2163T>A · rs2273666 · VCV1224161
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 51%, eas) — 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 0.15 | GERP 1.5, phastCons 0.99 |
| Overall | ||
| CADD | 7.014 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
51%
East Asian · 22,856/44,854 alleles
Filtering AF
50.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 50.2%
Overall
9.76%
157,545/1,613,810 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 51% | 2 |
| South Asian | 27.5% | 4 |
| Remaining individualsnot grpmax-eligible | 11.9% | 8 |
| Finnishnot grpmax-eligible | 11.8% | 8 |
| Ashkenazi Jewishnot grpmax-eligible | 10.5% | 10 |
| Admixed American | 10.4% | 10 |
| Middle Eastern | 6.88% | 15 |
| European (non-Finnish) | 6.86% | 15 |
| Amishnot grpmax-eligible | 6.58% | 15 |
| African / African-American | 5.16% | 19 |
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
- CDC5L
- Protein
- p.Leu721=
- Coding
- c.2163T>A
- MANE Select
- NM_001253
- dbSNP
- rs2273666
- Type
- single nucleotide variant
- Location
- chr6:44445726 (GRCh38)
- Gene constraint
- LOEUF 0.26 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.94 · 41 PDB
- Residue 721
- the 'interaction with plrg1' region; an α-helix
Similar variants
- CDC5L p.Ala93= Benign ★★ same type
- CDC5L p.Asp236= Benign ★★ same type
- CDC5L p.Ala234Val Uncertain significance ★ ⚠ same type
- CDC5L p.Ala457Thr Uncertain significance ★ ⚠ same type
- CDC5L p.Ala485Thr Uncertain significance ★ ⚠ same type
- CDC5L p.Arg202Lys Uncertain significance ★ ⚠ same type
- CDC5L p.Arg202Thr Uncertain significance ★ ⚠ same type
- CDC5L p.Arg321Cys 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/cdc5l-p-leu721 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown