SRMS p.Pro188=
c.564C>T · rs113866891 · VCV783873
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.75%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.34 | GERP -1.2, phastCons 0.082 |
| Overall | ||
| CADD | 5.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.75%
African / African-American · 3,563/75,066 alleles
Filtering AF
4.62%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.56%
Overall
0.308%
4,962/1,612,818 alleles · low-frequency
exomes 2,897/1,460,448 · genomes 2,065/152,370 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.75% | 21 |
| Ashkenazi Jewishnot grpmax-eligible | 0.838% | 119 |
| Middle Eastern | 0.545% | 184 |
| Remaining individualsnot grpmax-eligible | 0.451% | 222 |
| Admixed American | 0.355% | 282 |
| Finnishnot grpmax-eligible | 0.0733% | 1,364 |
| European (non-Finnish) | 0.0475% | 2,103 |
| South Asian | 0.0176% | 5,693 |
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
- SRMS
- Protein
- p.Pro188=
- Coding
- c.564C>T
- MANE Select
- NM_080823
- dbSNP
- rs113866891
- Type
- single nucleotide variant
- Location
- chr20:63543395 (GRCh38)
- Gene constraint
- LOEUF 1.445 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.99
- Residue 188
- the sh2 domain
Similar variants
- SRMS p.Pro382Leu Uncertain significance ★★ ⚠ same type
- SRMS p.Ala162Pro Uncertain significance ★ ⚠ same type
- SRMS p.Ala175Val Uncertain significance ★ ⚠ same type
- SRMS p.Ala199Thr Uncertain significance ★ ⚠ same type
- SRMS p.Ala449Gly Uncertain significance ★ ⚠ same type
- SRMS p.Ala453Val Uncertain significance ★ ⚠ same type
- SRMS p.Ala46Thr Uncertain significance ★ ⚠ same type
- SRMS p.Ala58Val 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/srms-p-pro188 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown