SMS p.Ser57=
c.171C>T · rs201558273 · VCV728106
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0331%, nfe)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.625 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.26 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 15.08 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0331%
European (non-Finnish) · 285/861,571 alleles
Filtering AF
0.0299%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0286%
Overall
0.0255%
299/1,171,026 alleles · ultra-rare
exomes 279/1,060,335 · genomes 20/110,691 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0331% | 3,023 |
| Remaining individualsnot grpmax-eligible | 0.0173% | 5,785 |
| African / African-American | 0.0107% | 9,335 |
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
- SMS
- Protein
- p.Ser57=
- Coding
- c.171C>T
- MANE Select
- NM_004595
- dbSNP
- rs201558273
- Type
- single nucleotide variant
- Location
- chrX:21971897 (GRCh38)
- Structure
- AlphaFold pLDDT 95.09 · 2 PDB
- Residue 57
- a modified residue (phosphoserine)
Similar variants
- SMS p.Arg234Ter Pathogenic/Likely pathogenic ★★ same condition
- SMS p.Gly56Ser Pathogenic ★★ ⚠ same condition
- SMS p.Pro112Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
- SMS p.Lys245Asn Uncertain significance ★★ ⚠ same condition
- SMS p.Ser184Asn Uncertain significance ★★ ⚠ same condition
- SMS p.Ala36Val Likely benign ★★ same condition
- SMS p.Glu187= Benign/Likely benign ★★ same condition
- SMS p.Pro281= Benign/Likely benign ★★ 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/sms-p-ser57 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown