SMS p.Ala127=
c.381C>T · rs764152466 · VCV2660158
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00217%, amr)
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 -2.3 | GERP -4.4 |
| Overall | ||
| CADD | 0.311 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00217%
Admixed American · 1/46,007 alleles
Filtering AF
0.000717%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000566%
Overall
0.00128%
14/1,095,007 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00217% | 46,007 |
| South Asian | 0.00176% | 56,889 |
| European (non-Finnish) | 0.00134% | 74,388 |
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.Ala127=
- Coding
- c.381C>T
- MANE Select
- NM_004595
- dbSNP
- rs764152466
- Type
- single nucleotide variant
- Location
- chrX:21977112 (GRCh38)
- Structure
- AlphaFold pLDDT 95.09 · 2 PDB
- Residue 127
- the pabs domain
Similar variants
- 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
- SMS c.661-4G>A 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-ala127 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown