Is MAPT p.Asp360= (c.1080C>T) pathogenic?

MAPT p.Asp360= (c.1080C>T) is classified Benign in MAPT (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-11-17). Common (popmax 18.2%, amr) — too common for a highly-penetrant pathogenic allele; Associated with frontotemporal dementia.

What condition is associated with MAPT p.Asp360= (c.1080C>T)?

MAPT p.Asp360= (c.1080C>T) is associated with frontotemporal dementia (ClinVar).

MAPT p.Asp360=

Q: How common is MAPT p.Asp360= (c.1080C>T) in the general population?

MAPT p.Asp360= (c.1080C>T) is common (popmax 18.2%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1080C>T · rs63750222 · VCV98199

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 18.2%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

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 -9.8	GERP -10
Overall
CADD	0.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.2% Admixed American · 10,904/60,028 alleles

Filtering AF 17.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.8%

Overall 11.9% 191,733/1,613,920 alleles · common exomes 175,487/1,461,680 · genomes 16,246/152,240 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	18.2%	6
East Asian	17.6%	6
Finnishnot grpmax-eligible	16.4%	6
European (non-Finnish)	12%	8
Remaining individualsnot grpmax-eligible	11.6%	9
Ashkenazi Jewishnot grpmax-eligible	9.6%	10
Middle Eastern	7.6%	13
South Asian	7.59%	13
Amishnot grpmax-eligible	5.81%	17
African / African-American	4.21%	24

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.Asp360=
Coding: c.1080C>T
MANE Select: NM_001377265
dbSNP: rs63750222
Type: single nucleotide variant
Location: chr17:45983659 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 360: 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

MAPT p.Asp360Asn 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-asp360 (accessed [today's date]).

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