MESP2 p.Pro259=
c.777G>A · rs762396354 · VCV1156599
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0039%, nfe)
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 Δ0.52 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.056 | GERP -4.2 |
| Overall | ||
| CADD | 9.146 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0039%
European (non-Finnish) · 46/1,179,962 alleles
Filtering AF
0.00299%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00267%
Overall
0.00291%
47/1,612,912 alleles · very rare
exomes 47/1,460,598 · genomes 0/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0039% | 25,651 |
| African / African-American | 0.00133% | 75,052 |
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
- MESP2
- Protein
- p.Pro259=
- Coding
- c.777G>A
- MANE Select
- NM_001039958
- dbSNP
- rs762396354
- Type
- single nucleotide variant
- Location
- chr15:89777134 (GRCh38)
- Gene constraint
- LOEUF 1.656 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.92
- Residue 259
- the 'disordered' region
Similar variants
- MESP2 p.Pro259fs Likely pathogenic ★ same residue
- MESP2 p.Gly77Ter Pathogenic/Likely pathogenic ★★ same type
- MESP2 p.Gly81Ter Pathogenic/Likely pathogenic ★★ same type
- MESP2 p.Ser39Ter Pathogenic/Likely pathogenic ★★ same type
- MESP2 p.Ser42Ter Pathogenic/Likely pathogenic ★★ same type
- MESP2 p.Ser4Ter Pathogenic/Likely pathogenic ★★ same type
- MESP2 c.*107T>C Uncertain significance ★★ same type
- MESP2 p.Ala360Thr 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/mesp2-p-pro259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown