MAPT p.Pro546=
c.1638G>A · rs201046056 · VCV323646
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.276%, 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 0.27 | GERP 2.4, phastCons 0.98 |
| Overall | ||
| CADD | 12.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.276%
East Asian · 124/44,882 alleles
Filtering AF
0.237%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.222%
Overall
0.0122%
197/1,614,190 alleles · rare
exomes 185/1,461,888 · genomes 12/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.276% | 362 |
| Admixed American | 0.08% | 1,250 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,814 |
| South Asian | 0.00329% | 30,359 |
| European (non-Finnish) | 0.0011% | 90,771 |
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.Pro546=
- Coding
- c.1638G>A
- MANE Select
- NM_001377265
- dbSNP
- rs201046056
- Type
- single nucleotide variant
- Location
- chr17:45991492 (GRCh38)
- Gene constraint
- LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.56 · 299 PDB
- Residue 546
- the 'disordered' region
Similar variants
- MAPT p.Pro546Leu Uncertain significance ★ ⚠ 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
- MAPT p.Asn671Lys Pathogenic ★★ ⚠ same condition
- MAPT p.Asn688= Pathogenic ★★ same condition
- MAPT p.Gln728His 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-pro546 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown