MTSS2 p.Ala189=
c.567G>A · VCV4681404
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.205%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -3.2 |
| Overall | ||
| CADD | 5.093 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.205%
East Asian · 92/44,872 alleles
Filtering AF
0.171%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.159%
Overall
0.0134%
216/1,612,580 alleles · rare
exomes 189/1,460,202 · genomes 27/152,378 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.205% | 488 |
| Finnishnot grpmax-eligible | 0.131% | 762 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,166 |
| South Asian | 0.00659% | 15,181 |
| European (non-Finnish) | 0.00169% | 58,999 |
| African / African-American | 0.00133% | 75,076 |
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
- MTSS2
- Protein
- p.Ala189=
- Coding
- c.567G>A
- MANE Select
- NM_138383
- Type
- single nucleotide variant
- Location
- chr16:70678309 (GRCh38)
- Gene constraint
- LOEUF 0.662 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.75
- Residue 189
- the imd domain
Similar variants
- MTSS2 p.Arg671Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- MTSS2 p.Arg734Cys Uncertain significance ★★ ⚠ same type
- MTSS2 p.Val368Ile Uncertain significance ★★ ⚠ same type
- MTSS2 p.Pro712= Likely benign ★★ same type
- MTSS2 p.Ser252= Benign ★★ same type
- MTSS2 p.Thr181= Likely benign ★★ same type
- MTSS2 c.291-6C>G Uncertain significance ★ same type
- MTSS2 c.291-8C>T 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/mtss2-p-ala189 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown