MAPT p.Pro146=
c.438G>A · rs3744459 · VCV3067576
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.015%, 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 -2.1 | GERP -4.3 |
| Overall | ||
| CADD | 1.529 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.015%
East Asian · 6/40,056 alleles
Filtering AF
0.00646%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00442%
Overall
0.000751%
11/1,465,008 alleles · ultra-rare
exomes 11/1,312,764 · genomes 0/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.015% | 6,676 |
| Finnishnot grpmax-eligible | 0.00201% | 49,696 |
| South Asian | 0.0014% | 71,478 |
| European (non-Finnish) | 0.000271% | 369,216 |
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
- MAPT
- Protein
- p.Pro146=
- Coding
- c.438G>A
- MANE Select
- NM_001377265
- dbSNP
- rs3744459
- Type
- single nucleotide variant
- Location
- chr17:45983017 (GRCh38)
- Gene constraint
- LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.56 · 299 PDB
- Residue 146
- the 'disordered' region
Similar variants
- MAPT c.1999-10G>T Pathogenic ★★ same type
- MAPT c.2091+16C>T Pathogenic ★★ same type
- MAPT c.2091+3G>A Pathogenic ★★ same type
- MAPT p.Arg798Trp Pathogenic ★★ ⚠ same type
- MAPT p.Asn671Lys Pathogenic ★★ ⚠ same type
- MAPT p.Asn688= Pathogenic ★★ same type
- MAPT p.Gln728His Pathogenic/Likely pathogenic ★★ ⚠ same type
- MAPT p.Gly727Ser Pathogenic/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/mapt-p-pro146 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown