Is MAPT p.Leu768Val (c.2302C>G) pathogenic?

MAPT p.Leu768Val (c.2302C>G) is classified Uncertain significance in MAPT (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-01). AlphaMissense: likely pathogenic (0.8726); Absent from gnomAD v4.1.

How common is MAPT p.Leu768Val (c.2302C>G) in the general population?

MAPT p.Leu768Val (c.2302C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPT p.Leu768Val (c.2302C>G)?

AlphaMissense predicts likely pathogenic (score 0.8726) — an in-silico prediction, not a clinical call.

MAPT p.Leu768Val

c.2302C>G · rs1598425089 · VCV808285

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8726 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8726	likely pathogenic
REVEL	0.196	benign-leaning
SaProt	LLR -11.19	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 5, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 9,855 bp · p 4.8e-09 · regional, not allelic
Overall
CADD	27.2	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 L693V vs ClinVar L768V) — 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.Leu768Val
Coding: c.2302C>G
MANE Select: NM_001377265
dbSNP: rs1598425089
Type: single nucleotide variant
Location: chr17:46023971 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 693 UniProt numbering: a β-strand

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

Similar variants

MAPT c.1999-10G>T Pathogenic ★★ same type
MAPT c.2091+16C>T Pathogenic ★★ same type
MAPT c.2091+3G>A Pathogenic ★★ same type
MAPT p.Arg798Trp Pathogenic ★★ ⚠ same type
MAPT p.Asn671Lys Pathogenic ★★ ⚠ same type
MAPT p.Asn688= Pathogenic ★★ same type
MAPT p.Gln728His Pathogenic/Likely pathogenic ★★ ⚠ same type
MAPT p.Gly727Ser Pathogenic/Likely pathogenic ★★ same type

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-leu768val (accessed [today's date]).

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