CGN p.Arg996Trp
c.2986C>T · rs144668349 · VCV3143925
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.536 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 2.5, phastCons 1 |
| Regional constraint | o/e 0.73 | unconstrained · MANE · 3,161 bp · p 9.1e-06 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,882 alleles
Filtering AF
0.000954%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000787%
Overall
0.00155%
25/1,613,260 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,441 |
| African / African-American | 0.00267% | 37,430 |
| Admixed American | 0.00167% | 59,982 |
| Finnishnot grpmax-eligible | 0.00156% | 64,006 |
| European (non-Finnish) | 0.00153% | 65,530 |
| South Asian | 0.0011% | 91,012 |
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.Arg996Trp
- Coding
- c.2986C>T
- MANE Select
- NM_020770
- dbSNP
- rs144668349
- Type
- single nucleotide variant
- Location
- chr1:151535123 (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-arg996trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown