Is MAPT p.Val701Phe (c.2101G>T) pathogenic?

MAPT p.Val701Phe (c.2101G>T) is classified Uncertain significance in MAPT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-22). AlphaMissense: likely pathogenic (0.7362); Absent from gnomAD v4.1; Associated with frontotemporal dementia.

What condition is associated with MAPT p.Val701Phe (c.2101G>T)?

MAPT p.Val701Phe (c.2101G>T) is associated with frontotemporal dementia (ClinVar).

How common is MAPT p.Val701Phe (c.2101G>T) in the general population?

MAPT p.Val701Phe (c.2101G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPT p.Val701Phe (c.2101G>T)?

AlphaMissense predicts likely pathogenic (score 0.7362) — an in-silico prediction, not a clinical call.

MAPT p.Val701Phe

c.2101G>T · rs2510187753 · VCV2038936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7362 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

frontotemporal dementia

Computational evidence

Protein change
AlphaMissense	0.7362	likely pathogenic
REVEL	0.752	pathogenic-leaning
SaProt	LLR -4.54	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 7.2, phastCons 1
Regional constraint	o/e 0.11	constrained · MANE · 3,912 bp · p 2.5e-06 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V626F vs ClinVar V701F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAPT
Protein: p.Val701Phe
Coding: c.2101G>T
MANE Select: NM_001377265
dbSNP: rs2510187753
Type: single nucleotide variant
Location: chr17:46014252 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 626 UniProt numbering: a β-strand; 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 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-val701phe (accessed [today's date]).

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