Is MAPT p.Glu86Asp (c.258A>C) pathogenic?

MAPT p.Glu86Asp (c.258A>C) is classified Uncertain significance in MAPT (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-17). AlphaMissense: likely benign (0.3391); Very rare (popmax 0.000509%, nfe); Associated with frontotemporal dementia.

What condition is associated with MAPT p.Glu86Asp (c.258A>C)?

MAPT p.Glu86Asp (c.258A>C) is associated with frontotemporal dementia (ClinVar).

How common is MAPT p.Glu86Asp (c.258A>C) in the general population?

MAPT p.Glu86Asp (c.258A>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about MAPT p.Glu86Asp (c.258A>C)?

AlphaMissense predicts likely benign (score 0.3391) — an in-silico prediction, not a clinical call.

MAPT p.Glu86Asp

c.258A>C · rs2072603923 · VCV1061335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3391 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

frontotemporal dementia

Computational evidence

Protein change
AlphaMissense	0.3391	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.46	GERP 0.78, phastCons 0.87
Regional constraint	o/e 0.90	unconstrained · MANE · 29 kb · p 0.0043 · regional, not allelic
Overall
CADD	19.43	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E115D vs ClinVar E86D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,178,992 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,612,042 alleles · very rare exomes 5/1,460,124 · genomes 1/151,918 · joint denominator

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.Glu86Asp
Coding: c.258A>C
MANE Select: NM_001377265
dbSNP: rs2072603923
Type: single nucleotide variant
Location: chr17:45978412 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 115 UniProt numbering: the 'disordered' region

Full MAPT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

frontotemporal dementia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STH p.Asn86Asp Likely benign ★ 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-glu86asp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown