Is MAPT p.Asp585fs (c.1749_1750del) pathogenic?

MAPT p.Asp585fs (c.17491750del) is classified Uncertain significance in MAPT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-03). No gnomAD frequency available for this variant; Associated with frontotemporal dementia.

What condition is associated with MAPT p.Asp585fs (c.1749_1750del)?

MAPT p.Asp585fs (c.1749_1750del) is associated with frontotemporal dementia (ClinVar).

How common is MAPT p.Asp585fs (c.1749_1750del) in the general population?

MAPT p.Asp585fs (c.1749_1750del) is no gnomAD frequency available for this variant (gnomAD).

MAPT p.Asp585fs

c.1749_1750del · rs2145830963 · VCV1509861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

frontotemporal dementia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 7.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAPT
Protein: p.Asp585fs
Coding: c.1749_1750del
MANE Select: NM_001377265
dbSNP: rs2145830963
Type: Deletion
Location: chr17:45996415 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 585: the 'microtubule-binding domain' 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

MAPT c.1733-3del Uncertain significance ★ same condition
MAPT c.220+5del Uncertain significance ★ same condition
MAPT p.Gln168fs Uncertain significance ★ same condition
MAPT p.Gly283fs Uncertain significance ★ same condition
MAPT p.Phe211fs Uncertain significance ★ same condition
MAPT c.1999-10G>T Pathogenic ★★ same condition
MAPT c.2091+16C>T Pathogenic ★★ same condition
MAPT c.2091+3G>A 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-asp585fs (accessed [today's date]).

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