MAPT p.Ala72=
c.216G>A · rs781640412 · VCV1945687
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
Conditions
1
frontotemporal dementia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.031 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -1.5 | GERP -2.4 |
| Overall | ||
| CADD | 11.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/60,000 alleles
Filtering AF
0.00543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0038%
Overall
0.00143%
23/1,613,796 alleles · ultra-rare
exomes 20/1,461,634 · genomes 3/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,571 |
| African / African-American | 0.00801% | 12,488 |
| South Asian | 0.0011% | 91,072 |
| European (non-Finnish) | 0.000763% | 131,099 |
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.Ala72=
- Coding
- c.216G>A
- MANE Select
- NM_001377265
- dbSNP
- rs781640412
- Type
- single nucleotide variant
- Location
- chr17:45971941 (GRCh38)
- Gene constraint
- LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.56 · 299 PDB
- Residue 72
- the 'disordered' region
Similar variants
- 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
- MAPT p.Asn671Lys Pathogenic ★★ ⚠ same condition
- MAPT p.Asn688= Pathogenic ★★ same condition
- MAPT p.Gln728His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MAPT p.Gly727Ser Pathogenic/Likely 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-ala72 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown