SMS p.Pro281=
c.843A>G · rs144489522 · VCV1763378
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.204%, afr)
Conditions
1
Inborn genetic diseases
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 -1.3 | GERP -4.4 |
| Overall | ||
| CADD | 2.088 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.204%
African / African-American · 115/56,394 alleles
Filtering AF
0.174%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.162%
Overall
0.0117%
136/1,161,688 alleles · rare
exomes 64/1,049,534 · genomes 72/112,154 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.204% | 490 |
| Admixed American | 0.0241% | 4,153 |
| Middle Eastern | 0.0237% | 4,220 |
| Remaining individualsnot grpmax-eligible | 0.0087% | 11,500 |
| European (non-Finnish) | 0.000588% | 170,207 |
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.Pro281=
- Coding
- c.843A>G
- MANE Select
- NM_004595
- dbSNP
- rs144489522
- Type
- single nucleotide variant
- Location
- chrX:21984396 (GRCh38)
- Structure
- AlphaFold pLDDT 95.09 · 2 PDB
- Residue 281
- the pabs domain
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.Ser101Gly 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-pro281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown