Is MAPT p.Thr39= (c.117G>A) pathogenic?

MAPT p.Thr39= (c.117G>A) is classified Benign/Likely benign in MAPT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-28). Ultra-rare (popmax 0.0374%, sas); Associated with frontotemporal dementia.

What condition is associated with MAPT p.Thr39= (c.117G>A)?

MAPT p.Thr39= (c.117G>A) is associated with frontotemporal dementia (ClinVar).

How common is MAPT p.Thr39= (c.117G>A) in the general population?

MAPT p.Thr39= (c.117G>A) is ultra-rare (popmax 0.0374%, sas) (gnomAD).

MAPT p.Thr39=

c.117G>A · rs63750529 · VCV98195

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0374%, sas)

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 -1.5	GERP -4.7
Overall
CADD	4.766	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0374% South Asian · 34/90,940 alleles

Filtering AF 0.0274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0241%

Overall 0.0929% 1,498/1,612,716 alleles · ultra-rare exomes 1,276/1,460,416 · genomes 222/152,300 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.66%	60
Remaining individualsnot grpmax-eligible	0.119%	843
South Asiangrpmax	0.0374%	2,675
European (non-Finnish)	0.0271%	3,687
African / African-American	0.00533%	18,749
East Asian	0.00446%	22,438
Admixed American	0.00167%	59,996

Finnish 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.Thr39=
Coding: c.117G>A
MANE Select: NM_001377265
dbSNP: rs63750529
Type: single nucleotide variant
Location: chr17:45962454 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 39: 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.Thr39Met Uncertain significance ★ ⚠ same residue
STH p.Met39Ile Uncertain significance ★ ⚠ 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

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-thr39 (accessed [today's date]).

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