CGN p.Val508Leu
c.1522G>T · rs1042958096 · VCV3143913
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0194%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.407 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 16 kb · p 0.38 · regional, not allelic |
| Overall | ||
| CADD | 26.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0194%
Middle Eastern · 1/5,164 alleles
Filtering AF
0.00157%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00134%
Overall
0.00174%
28/1,612,748 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0194% | 5,164 |
| European (non-Finnish) | 0.00229% | 43,702 |
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
- CGN
- Protein
- p.Val508Leu
- Coding
- c.1522G>T
- MANE Select
- NM_020770
- dbSNP
- rs1042958096
- Type
- single nucleotide variant
- Location
- chr1:151524794 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.44
Similar variants
- CGN p.Ala357= Benign/Likely benign ★★ same type
- CGN p.Arg11Trp Likely benign ★★ same type
- CGN p.Arg227Trp Likely benign ★★ same type
- CGN p.Arg547Lys Benign ★★ same type
- CGN p.Arg973Gln Benign ★★ same type
- CGN p.Glu771Lys Benign/Likely benign ★★ same type
- CGN p.Ile60= Benign ★★ same type
- CGN p.Ala1035Thr 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/cgn-p-val508leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown