MTSS2 p.Pro719=
c.2157G>A · VCV4533644
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0342%, afr)
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 -11 | GERP -3.3 |
| Overall | ||
| CADD | 0.514 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0342%
African / African-American · 25/73,056 alleles
Filtering AF
0.0237%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0203%
Overall
0.00605%
93/1,537,686 alleles · ultra-rare
exomes 68/1,385,370 · genomes 25/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0342% | 2,922 |
| East Asian | 0.0146% | 6,855 |
| Remaining individualsnot grpmax-eligible | 0.0117% | 8,514 |
| South Asian | 0.0108% | 9,233 |
| Admixed American | 0.00598% | 16,725 |
| European (non-Finnish) | 0.00376% | 26,620 |
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.Pro719=
- Coding
- c.2157G>A
- MANE Select
- NM_138383
- Type
- single nucleotide variant
- Location
- chr16:70663764 (GRCh38)
- Gene constraint
- LOEUF 0.662 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.75
- Residue 719
- the wh2 domain; the 'disordered' region
Similar variants
- MTSS2 p.Pro719Arg Uncertain significance ★ ⚠ same residue
- MTSS2 p.Pro719Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro719 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown