SMS p.Lys214=
c.642G>A · VCV4949286
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.046%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.782 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.23 | donor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP 9.8 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 12.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.046%
Middle Eastern · 2/4,351 alleles
Filtering AF
0.00813%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0034%
Overall
0.0021%
23/1,096,121 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.046% | 2,176 |
| South Asian | 0.0105% | 9,499 |
| Remaining individualsnot grpmax-eligible | 0.0063% | 15,865 |
| European (non-Finnish) | 0.00134% | 74,475 |
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.Lys214=
- Coding
- c.642G>A
- MANE Select
- NM_004595
- Type
- single nucleotide variant
- Location
- chrX:21978096 (GRCh38)
- Structure
- AlphaFold pLDDT 95.09 · 2 PDB
- Residue 214
- the pabs domain; a β-strand
Similar variants
- SMS p.Lys214del Uncertain significance ★ same residue
- SMS p.Arg234Ter Pathogenic/Likely pathogenic ★★ same type
- SMS p.Gly203Asp Pathogenic ★★ same type
- SMS p.Gly56Ser Pathogenic ★★ ⚠ same type
- SMS p.Ile196Thr Likely pathogenic ★★ same type
- SMS p.Pro112Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
- SMS c.1061+2T>C Uncertain significance ★★ same type
- SMS c.505+3A>G 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/sms-p-lys214 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown