CGN p.Arg221Trp
c.661C>T · VCV4653112
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.137 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.81 | GERP -1.4, phastCons 0.86 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 16 kb · p 0.38 · regional, not allelic |
| Overall | ||
| CADD | 22.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,088 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.000753%
11/1,461,756 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,181 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| African / African-American | 0.00133% | 75,074 |
| European (non-Finnish) | 0.000169% | 590,026 |
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.Arg221Trp
- Coding
- c.661C>T
- MANE Select
- NM_020770
- Type
- single nucleotide variant
- Location
- chr1:151519180 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.44
- Residue 221
- the 'head' region; the 'disordered' region
Similar variants
- CGN p.Arg221Gln Uncertain significance ★ same residue
- 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
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-arg221trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown