MAPT p.Pro693=
c.2079G>A · rs63751395 · VCV98216
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0575%, eas)
Conditions
2
MAPT-Related Spectrum Disorders
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 -0.44 | GERP -7.2, phastCons 0.001 |
| Overall | ||
| CADD | 11.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0575%
East Asian · 25/43,450 alleles
Filtering AF
0.0399%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0342%
Overall
0.00445%
70/1,574,224 alleles · ultra-rare
exomes 55/1,421,944 · genomes 15/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0575% | 1,738 |
| African / African-American | 0.0336% | 2,977 |
| Middle Eastern | 0.0334% | 2,996 |
| South Asian | 0.0035% | 28,554 |
| Remaining individualsnot grpmax-eligible | 0.00327% | 30,543 |
| Admixed American | 0.00185% | 53,920 |
| Finnishnot grpmax-eligible | 0.00163% | 61,336 |
| European (non-Finnish) | 0.000949% | 105,323 |
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.Pro693=
- Coding
- c.2079G>A
- MANE Select
- NM_001377265
- dbSNP
- rs63751395
- Type
- single nucleotide variant
- Location
- chr17:46010390 (GRCh38)
- Gene constraint
- LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.56 · 299 PDB
- Residue 693
- a β-strand
Similar variants
- MAPT p.Pro693Leu Pathogenic ★★ same residue
- MAPT p.Pro693Ser Likely pathogenic ★★ same residue
- MAPT p.Pro693Arg Uncertain significance ★ ⚠ same residue
- MAPT p.Pro693Ala Likely pathogenic ★ same residue
- MAPT c.1999-10G>T Pathogenic ★★ same condition
- MAPT c.2091+16C>T Pathogenic ★★ same condition
- MAPT c.2091+3G>A Pathogenic ★★ same condition
- MAPT p.Arg798Trp Pathogenic ★★ ⚠ same condition
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-pro693 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown