Is MAPT p.Ser788= (c.2364G>A) pathogenic?

MAPT p.Ser788= (c.2364G>A) is classified Conflicting classifications of pathogenicity in MAPT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-13). Very rare (popmax 0.00627%, nfe); Associated with MAPT-Related Spectrum Disorders.

What condition is associated with MAPT p.Ser788= (c.2364G>A)?

MAPT p.Ser788= (c.2364G>A) is associated with MAPT-Related Spectrum Disorders, frontotemporal dementia (ClinVar).

How common is MAPT p.Ser788= (c.2364G>A) in the general population?

MAPT p.Ser788= (c.2364G>A) is very rare (popmax 0.00627%, nfe) (gnomAD).

MAPT p.Ser788=

c.2364G>A · rs377720312 · VCV425138

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00627%, nfe)

Conditions

MAPT-Related Spectrum Disorders

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 -3.7	GERP -14
Overall
CADD	4.642	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00627% European (non-Finnish) · 74/1,180,048 alleles

Filtering AF 0.00511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00502% 81/1,613,968 alleles · very rare exomes 78/1,461,842 · genomes 3/152,126 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00627%	15,947
Finnishnot grpmax-eligible	0.00469%	21,327
African / African-American	0.00267%	37,443
East Asian	0.00223%	44,886
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Ser788=
Coding: c.2364G>A
MANE Select: NM_001377265
dbSNP: rs377720312
Type: single nucleotide variant
Location: chr17:46024033 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB

Full MAPT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MAPT-Related Spectrum Disorders

Also linked: frontotemporal dementia

Similar variants

MAPT p.Ser788Leu 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-ser788 (accessed [today's date]).

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