Is MAPT p.Glu12= (c.36A>G) pathogenic?

MAPT p.Glu12= (c.36A>G) is classified Likely benign in MAPT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-14). Very rare (popmax 0.00119%, nfe); Associated with frontotemporal dementia.

What condition is associated with MAPT p.Glu12= (c.36A>G)?

MAPT p.Glu12= (c.36A>G) is associated with frontotemporal dementia (ClinVar).

How common is MAPT p.Glu12= (c.36A>G) in the general population?

MAPT p.Glu12= (c.36A>G) is very rare (popmax 0.00119%, nfe) (gnomAD).

MAPT p.Glu12=

c.36A>G · rs375852870 · VCV1661803

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

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 0.56	GERP -4, phastCons 0.92
Overall
CADD	2.994	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,914 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00093% 15/1,612,374 alleles · very rare exomes 12/1,460,294 · genomes 3/152,080 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,348
European (non-Finnish)grpmax	0.00119%	84,279

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu12=
Coding: c.36A>G
MANE Select: NM_001377265
dbSNP: rs375852870
Type: single nucleotide variant
Location: chr17:45962373 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 12: 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-glu12 (accessed [today's date]).

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