Is MAP3K13 p.Glu499fs (c.1496_1497insTCCT) pathogenic?

MAP3K13 p.Glu499fs (c.14961497insTCCT) is classified Uncertain significance in MAP3K13 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-12). Very rare (popmax 8.49e-05%, nfe).

How common is MAP3K13 p.Glu499fs (c.1496_1497insTCCT) in the general population?

MAP3K13 p.Glu499fs (c.1496_1497insTCCT) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

MAP3K13 p.Glu499fs

c.1496_1497insTCCT · VCV4965333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,462 alleles

Overall 6.85e-05% 1/1,459,006 alleles · very rare

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: MAP3K13
Protein: p.Glu499fs
Coding: c.1496_1497insTCCT
MANE Select: NM_004721
Type: Insertion
Location: chr3:185465854 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.92
Residue 499: the 'leucine-zipper 2' region

Full MAP3K13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/map3k13-p-glu499fs (accessed [today's date]).

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