MAPRE2 p.Leu101=
c.303G>A · VCV3339046
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, 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 10 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 13.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,886 alleles
Filtering AF
0.00726%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00514%
Overall
0.00136%
22/1,613,796 alleles · ultra-rare
exomes 21/1,461,592 · genomes 1/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,412 |
| South Asian | 0.00329% | 30,357 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| Finnishnot grpmax-eligible | 0.00156% | 64,022 |
| European (non-Finnish) | 0.000848% | 117,987 |
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
- MAPRE2
- Protein
- p.Leu101=
- Coding
- c.303G>A
- MANE Select
- NM_014268
- Type
- single nucleotide variant
- Location
- chr18:35097498 (GRCh38)
- Gene constraint
- LOEUF 0.494 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 75.12
- Residue 101
- the calponin-homology (ch) domain
Similar variants
- MAPRE2 p.Arg143Cys Pathogenic/Likely pathogenic ★★ same type
- MAPRE2 p.Glu318Lys Uncertain significance ★★ ⚠ same type
- MAPRE2 p.Ser28Ter Uncertain significance ★★ same type
- MAPRE2 c.250+8A>T Benign/Likely benign ★★ same type
- MAPRE2 p.Gly260= Benign ★★ same type
- MAPRE2 p.His282= Benign/Likely benign ★★ same type
- MAPRE2 p.Pro322= Benign ★★ same type
- MAPRE2 p.Arg173Gln Likely pathogenic ★ 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/mapre2-p-leu101 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown