MAPT p.Val618=
c.1854G>A · rs114900761 · VCV1569130
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.056%, afr)
Conditions
1
frontotemporal dementia
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 3.8 | GERP 3.7, phastCons 1 |
| Overall | ||
| CADD | 9.455 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.056%
African / African-American · 42/75,022 alleles
Filtering AF
0.0425%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0378%
Overall
0.00273%
44/1,613,592 alleles · ultra-rare
exomes 17/1,461,374 · genomes 27/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.056% | 1,786 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| European (non-Finnish) | 8.48e-05% | 1,179,848 |
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.Val618=
- Coding
- c.1854G>A
- MANE Select
- NM_001377265
- dbSNP
- rs114900761
- Type
- single nucleotide variant
- Location
- chr17:45996520 (GRCh38)
- Gene constraint
- LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.56 · 299 PDB
- Residue 618
- a UniProt-annotated variant site (in ftd1; most common mutation; reduction in the ability to promote microtubule assembly; accelerates aggregation of tau into filaments); a UniProt-annotated variant site (in ftd1 and cbd; reduction in the ability to promote microtubule assembly); a β-strand; the 'microtubule-binding domain' 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-val618 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown