Is MAPT p.Pro304= (c.912C>G) pathogenic?

MAPT p.Pro304= (c.912C>G) is classified Benign/Likely benign in MAPT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). Rare (popmax 0.363%, afr); Associated with frontotemporal dementia.

What condition is associated with MAPT p.Pro304= (c.912C>G)?

MAPT p.Pro304= (c.912C>G) is associated with frontotemporal dementia (ClinVar).

How common is MAPT p.Pro304= (c.912C>G) in the general population?

MAPT p.Pro304= (c.912C>G) is rare (popmax 0.363%, afr) (gnomAD).

MAPT p.Pro304=

c.912C>G · rs142327009 · VCV703938

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.363%, afr)

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 -0.23	GERP 0.47, phastCons 0.005
Overall
CADD	0.598	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.363% African / African-American · 272/75,012 alleles

Filtering AF 0.327% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.313%

Overall 0.0257% 415/1,611,928 alleles · rare exomes 206/1,459,630 · genomes 209/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.363%	276
East Asian	0.154%	650
Admixed American	0.045%	2,221
Remaining individualsnot grpmax-eligible	0.032%	3,121
European (non-Finnish)	0.00229%	43,678

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.Pro304=
Coding: c.912C>G
MANE Select: NM_001377265
dbSNP: rs142327009
Type: single nucleotide variant
Location: chr17:45983491 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 304: the 'disordered' 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-pro304 (accessed [today's date]).

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