SMC3 p.Val528=
c.1584T>C · rs1445912504 · VCV2167284
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00102%, nfe)
Conditions
1
Cornelia de Lange syndrome 3
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3 | GERP 0.53, phastCons 1 |
| Overall | ||
| CADD | 11.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00102%
European (non-Finnish) · 12/1,179,916 alleles
Filtering AF
0.000542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000428%
Overall
0.000744%
12/1,613,960 alleles · very rare
exomes 6/1,461,684 · genomes 6/152,276 · joint denominator
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
- SMC3
- Protein
- p.Val528=
- Coding
- c.1584T>C
- MANE Select
- NM_005445
- dbSNP
- rs1445912504
- Type
- single nucleotide variant
- Location
- chr10:110590486 (GRCh38)
- Gene constraint
- LOEUF 0.132 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.37 · 12 PDB
- Residue 528
- an α-helix
Similar variants
- 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
- SMC3 p.Arg520Ser 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-val528 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown