Is MAPT p.Arg413Gln (c.1238G>A) pathogenic?

MAPT p.Arg413Gln (c.1238G>A) is classified Likely benign in MAPT (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.0662); Very rare (popmax 0.00334%, amr).

How common is MAPT p.Arg413Gln (c.1238G>A) in the general population?

MAPT p.Arg413Gln (c.1238G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about MAPT p.Arg413Gln (c.1238G>A)?

AlphaMissense predicts likely benign (score 0.0662) — an in-silico prediction, not a clinical call.

MAPT p.Arg413Gln

c.1238G>A · rs1261221296 · VCV731963

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0662 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0662	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5	GERP -8.7
Regional constraint	o/e 0.90	unconstrained · MANE · 29 kb · p 0.0043 · regional, not allelic
Overall
CADD	0.003	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 R338Q vs ClinVar R413Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,860 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000744% 12/1,612,900 alleles · very rare exomes 8/1,460,696 · genomes 4/152,204 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,930
East Asian	0.00223%	44,892
South Asian	0.0011%	91,056
European (non-Finnish)	0.000678%	147,484

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.Arg413Gln
Coding: c.1238G>A
MANE Select: NM_001377265
dbSNP: rs1261221296
Type: single nucleotide variant
Location: chr17:45983817 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 49.56 · 299 PDB
Residue 338 UniProt numbering: the 'disordered' region

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

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MAPT p.Asn688= Pathogenic ★★ same type
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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-arg413gln (accessed [today's date]).

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