Is MAPT p.Asp40= (c.120C>T) pathogenic?

MAPT p.Asp40= (c.120C>T) is classified Benign/Likely benign in MAPT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-01). Rare (popmax 0.315%, amr); Associated with frontotemporal dementia.

What condition is associated with MAPT p.Asp40= (c.120C>T)?

MAPT p.Asp40= (c.120C>T) is associated with frontotemporal dementia (ClinVar).

How common is MAPT p.Asp40= (c.120C>T) in the general population?

MAPT p.Asp40= (c.120C>T) is rare (popmax 0.315%, amr) (gnomAD).

MAPT p.Asp40=

c.120C>T · rs191362093 · VCV695504

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.315%, amr)

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 -0.12	GERP 0.78, phastCons 0.007
Overall
CADD	7.379	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.315% Admixed American · 189/59,986 alleles

Filtering AF 0.278% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.264%

Overall 0.0136% 219/1,612,682 alleles · rare exomes 122/1,460,394 · genomes 97/152,288 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.315%	317
Middle Eastern	0.0196%	5,092
Remaining individualsnot grpmax-eligible	0.016%	6,238
African / African-American	0.00267%	37,505
East Asian	0.00223%	44,876
European (non-Finnish)	0.00127%	78,660
South Asian	0.0011%	90,920

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.Asp40=
Coding: c.120C>T
MANE Select: NM_001377265
dbSNP: rs191362093
Type: single nucleotide variant
Location: chr17:45962457 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 40: 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 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-asp40 (accessed [today's date]).

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