Is MAPT p.Asp54= (c.162C>T) pathogenic?

MAPT p.Asp54= (c.162C>T) is classified Uncertain significance in MAPT (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.029%, eas); Associated with MAPT-Related Spectrum Disorders.

What condition is associated with MAPT p.Asp54= (c.162C>T)?

MAPT p.Asp54= (c.162C>T) is associated with MAPT-Related Spectrum Disorders (ClinVar).

How common is MAPT p.Asp54= (c.162C>T) in the general population?

MAPT p.Asp54= (c.162C>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

MAPT p.Asp54=

c.162C>T · rs750428288 · VCV889715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

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	all four deltas below 0.2 · C>G here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.1	GERP -3.1
Overall
CADD	2.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,886 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00118% 19/1,613,896 alleles · ultra-rare exomes 15/1,461,736 · genomes 4/152,160 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,453
Middle Eastern	0.0164%	6,084
African / African-American	0.004%	24,971
European (non-Finnish)	0.00017%	589,971

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.Asp54=
Coding: c.162C>T
MANE Select: NM_001377265
dbSNP: rs750428288
Type: single nucleotide variant
Location: chr17:45971887 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 54: the 'disordered' region

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

Disease context

MAPT-Related Spectrum Disorders

Similar variants

MAPT p.Asn671Lys Pathogenic ★★ ⚠ same condition
MAPT p.Ile784Val Uncertain significance ★★ ⚠ same condition
MAPT c.220+2450A>G Likely benign ★★ same condition
MAPT c.-133C>A Benign ★★ same condition
MAPT c.-13A>G Benign ★★ same condition
MAPT c.-285A>G Benign ★★ same condition
MAPT c.*1067T>C Benign ★★ same condition
MAPT c.*1101A>G Benign ★★ 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-asp54 (accessed [today's date]).

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