Is MAPT p.Lys672Arg (c.2015A>G) pathogenic?

MAPT p.Lys672Arg (c.2015A>G) is classified Uncertain significance in MAPT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: likely benign (0.229); No allele count reported in gnomAD v4.1 (AN 1,575,192); Associated with frontotemporal dementia.

What condition is associated with MAPT p.Lys672Arg (c.2015A>G)?

MAPT p.Lys672Arg (c.2015A>G) is associated with frontotemporal dementia (ClinVar).

How common is MAPT p.Lys672Arg (c.2015A>G) in the general population?

MAPT p.Lys672Arg (c.2015A>G) is no allele count reported in gnomAD v4.1 (AN 1,575,192) (gnomAD).

What do computational predictors say about MAPT p.Lys672Arg (c.2015A>G)?

AlphaMissense predicts likely benign (score 0.229) — an in-silico prediction, not a clinical call.

MAPT p.Lys672Arg

c.2015A>G · VCV3640349

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.229 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,575,192)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

frontotemporal dementia

Computational evidence

Protein change
AlphaMissense	0.229	likely benign
REVEL	0.794	moderately pathogenic-leaning
SaProt	LLR -9.22	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.26	acceptor loss, 16 bp away · masked 0 · deltas
Pangolin	Δ0.31	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 7.1, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 14 kb · p 0.016 · regional, not allelic
Overall
CADD	25.4	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 K597R vs ClinVar K672R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,575,192). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAPT
Protein: p.Lys672Arg
Coding: c.2015A>G
MANE Select: NM_001377265
Type: single nucleotide variant
Location: chr17:46010326 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 597 UniProt numbering: a UniProt-annotated variant site (in ftd1); 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-lys672arg (accessed [today's date]).

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