MAPT p.Ser226=
c.678C>T · rs537438059 · VCV770025
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0629%, sas)
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 -3.5 | GERP -2.6 |
| Overall | ||
| CADD | 5.857 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0629%
South Asian · 56/89,068 alleles
Filtering AF
0.0497%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0449%
Overall
0.004%
64/1,600,496 alleles · ultra-rare
exomes 62/1,448,292 · genomes 2/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0629% | 1,591 |
| Remaining individualsnot grpmax-eligible | 0.00807% | 12,394 |
| African / African-American | 0.00134% | 74,866 |
| European (non-Finnish) | 0.00017% | 586,892 |
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.Ser226=
- Coding
- c.678C>T
- MANE Select
- NM_001377265
- dbSNP
- rs537438059
- Type
- single nucleotide variant
- Location
- chr17:45983257 (GRCh38)
- Gene constraint
- LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.56 · 299 PDB
- Residue 226
- the 'disordered' region
Similar variants
- MAPT p.Ser226Tyr Uncertain significance ★ ⚠ same residue
- 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
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-ser226 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown