Is MAPT p.Pro568= (c.1704G>T) pathogenic?

MAPT p.Pro568= (c.1704G>T) is classified Likely benign in MAPT (ClinVar, Single submitter, 2 submitters; last evaluated 2022-07-05). Ultra-rare (popmax 0.0703%, sas); Associated with frontotemporal dementia.

What condition is associated with MAPT p.Pro568= (c.1704G>T)?

MAPT p.Pro568= (c.1704G>T) is associated with frontotemporal dementia (ClinVar).

How common is MAPT p.Pro568= (c.1704G>T) in the general population?

MAPT p.Pro568= (c.1704G>T) is ultra-rare (popmax 0.0703%, sas) (gnomAD).

MAPT p.Pro568=

c.1704G>T · rs1052551 · VCV1630372

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0703%, 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 -5.5	GERP -11
Overall
CADD	0.106	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0703% South Asian · 64/91,082 alleles

Filtering AF 0.0565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0514%

Overall 0.00415% 67/1,613,900 alleles · ultra-rare exomes 65/1,461,852 · genomes 2/152,048 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0703%	1,423
Remaining individualsnot grpmax-eligible	0.0032%	31,235
East Asian	0.00223%	44,892

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.Pro568=
Coding: c.1704G>T
MANE Select: NM_001377265
dbSNP: rs1052551
Type: single nucleotide variant
Location: chr17:45991558 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 568: the 'disordered' region; 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 p.Pro568Leu 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
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-pro568 (accessed [today's date]).

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