Is MAPT p.Ser630= (c.1890C>T) pathogenic?

MAPT p.Ser630= (c.1890C>T) is classified Likely benign in MAPT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-18). Very rare (popmax 0.00934%, afr); Associated with frontotemporal dementia.

What condition is associated with MAPT p.Ser630= (c.1890C>T)?

MAPT p.Ser630= (c.1890C>T) is associated with frontotemporal dementia (ClinVar).

How common is MAPT p.Ser630= (c.1890C>T) in the general population?

MAPT p.Ser630= (c.1890C>T) is very rare (popmax 0.00934%, afr) (gnomAD).

MAPT p.Ser630=

c.1890C>T · rs372356754 · VCV2086260

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Conditions

frontotemporal dementia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.27	GERP -1.2, phastCons 0.82
Overall
CADD	10.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,932 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00174% 28/1,613,508 alleles · very rare exomes 24/1,461,294 · genomes 4/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,705
South Asian	0.0033%	30,329
East Asian	0.00223%	44,882
European (non-Finnish)	0.00144%	69,402

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.Ser630=
Coding: c.1890C>T
MANE Select: NM_001377265
dbSNP: rs372356754
Type: single nucleotide variant
Location: chr17:45996556 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 630: 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-ser630 (accessed [today's date]).

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