MAPRE2 p.Leu272=
c.814T>C · rs375818634 · VCV746733
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.028%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -3.8, phastCons 0.002 |
| Overall | ||
| CADD | 6.026 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.028%
African / African-American · 21/74,926 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.00527%
85/1,614,100 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.028% | 3,568 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,811 |
| East Asian | 0.00445% | 22,451 |
| European (non-Finnish) | 0.00432% | 23,138 |
| Admixed American | 0.00333% | 30,001 |
| South Asian | 0.0011% | 91,092 |
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.Leu272=
- Coding
- c.814T>C
- MANE Select
- NM_014268
- dbSNP
- rs375818634
- Type
- single nucleotide variant
- Location
- chr18:35132095 (GRCh38)
- Gene constraint
- LOEUF 0.494 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 75.12
- Residue 272
- the eb1 c-terminal domain; the 'dctn1-binding' region; the 'apc-binding' region
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-leu272 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown