SMC3 p.Arg221Ter
c.661C>T · rs1564789897 · VCV581922
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Cornelia de Lange syndrome 3
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 9 of 29 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP 0.82, phastCons 1 |
| Overall | ||
| CADD | 37.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- SMC3
- Protein
- p.Arg221Ter
- Coding
- c.661C>T
- MANE Select
- NM_005445
- dbSNP
- rs1564789897
- Type
- single nucleotide variant
- Location
- chr10:110582036 (GRCh38)
- Gene constraint
- LOEUF 0.132 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.37 · 12 PDB
Similar variants
- SMC3 p.Arg221Gln Uncertain significance ★ ⚠ same residue
- SMC3 p.Gln1147Glu Pathogenic ★★ same condition
- SMC3 p.Glu95Lys Likely pathogenic ★★ same condition
- SMC3 p.Ile196Thr Pathogenic/Likely pathogenic ★★ same condition
- SMC3 p.Met648Val Pathogenic/Likely pathogenic ★★ same condition
- SMC3 p.Trp473Gly Likely pathogenic ★★ same condition
- SMC3 c.430-3T>C Uncertain significance ★★ same condition
- SMC3 p.Ala484Gly Uncertain significance ★★ ⚠ same condition
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/smc3-p-arg221ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown