CGN p.Arg493Trp
c.1477C>T · rs754175873 · VCV2518701
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.531 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP 1.2, phastCons 1 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 16 kb · p 0.38 · regional, not allelic |
| Overall | ||
| CADD | 25.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
East Asian · 9/44,848 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0078%
Overall
0.00254%
41/1,611,048 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0201% | 4,983 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00678% | 14,747 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,770 |
| European (non-Finnish) | 0.00212% | 47,176 |
| Finnishnot grpmax-eligible | 0.00156% | 63,940 |
| African / African-American | 0.00134% | 74,816 |
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.Arg493Trp
- Coding
- c.1477C>T
- MANE Select
- NM_020770
- dbSNP
- rs754175873
- Type
- single nucleotide variant
- Location
- chr1:151524749 (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-arg493trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown