MAPT p.Ser393=
c.1179G>A · rs139144750 · VCV3031249
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Conditions
1
MAPT-related disorder
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 -2.5 | GERP -9.9 |
| Overall | ||
| CADD | 0.582 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,878 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000474%
Overall
0.00105%
17/1,613,990 alleles · very rare
exomes 16/1,461,754 · genomes 1/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,439 |
| African / African-American | 0.00267% | 37,475 |
| European (non-Finnish) | 0.0011% | 90,769 |
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.Ser393=
- Coding
- c.1179G>A
- MANE Select
- NM_001377265
- dbSNP
- rs139144750
- Type
- single nucleotide variant
- Location
- chr17:45983758 (GRCh38)
- Gene constraint
- LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.56 · 299 PDB
- Residue 393
- the 'disordered' region
Disease context
MAPT-related disorder
Similar variants
- MAPT p.Ser393Leu Benign ★★ same residue
- MAPT p.Asn671Lys Pathogenic ★★ ⚠ same condition
- MAPT p.Ile784Val Uncertain significance ★★ ⚠ same condition
- MAPT c.220+2450A>G Likely benign ★★ same condition
- MAPT c.-133C>A Benign ★★ same condition
- MAPT c.-13A>G Benign ★★ same condition
- MAPT c.-285A>G Benign ★★ same condition
- MAPT c.*1067T>C Benign ★★ 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-ser393 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown