Is MAP3K13 p.Glu44Lys (c.130G>A) pathogenic?

MAP3K13 p.Glu44Lys (c.130G>A) is classified Likely benign in MAP3K13 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-11-01). AlphaMissense: likely benign (0.0774); Rare (popmax 0.555%, nfe).

How common is MAP3K13 p.Glu44Lys (c.130G>A) in the general population?

MAP3K13 p.Glu44Lys (c.130G>A) is rare (popmax 0.555%, nfe) (gnomAD).

What do computational predictors say about MAP3K13 p.Glu44Lys (c.130G>A)?

AlphaMissense predicts likely benign (score 0.0774) — an in-silico prediction, not a clinical call.

MAP3K13 p.Glu44Lys

c.130G>A · rs35266179 · VCV2654329

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0774 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.555%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0774	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 0.078, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 381 bp · p 0.77 · regional, not allelic
Overall
CADD	14.59	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.555% European (non-Finnish) · 6,552/1,180,016 alleles

Filtering AF 0.544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.539%

Overall 0.463% 7,468/1,614,150 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.54%	65
Ashkenazi Jewishnot grpmax-eligible	0.655%	153
European (non-Finnish)grpmax	0.555%	180
Finnishnot grpmax-eligible	0.534%	187
Remaining individualsnot grpmax-eligible	0.357%	280
Admixed American	0.128%	779
African / African-American	0.0759%	1,317
Middle Eastern	0.0495%	2,020
South Asian	0.00659%	15,180

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu44Lys
Coding: c.130G>A
MANE Select: NM_004721
dbSNP: rs35266179
Type: single nucleotide variant
Location: chr3:185428711 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.92
Residue 44: the 'disordered' region; a UniProt-annotated variant site (in)

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

Similar variants

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MAP3K13 p.Ala465Thr Uncertain significance ★ ⚠ same type
MAP3K13 p.Ala96Val Uncertain significance ★ ⚠ same type
MAP3K13 p.Arg278His Uncertain significance ★ ⚠ same type
MAP3K13 p.Arg326Trp Uncertain significance ★ ⚠ same type
MAP3K13 p.Arg401Gln Uncertain significance ★ ⚠ same type
MAP3K13 p.Arg449Gln Uncertain significance ★ same type
MAP3K13 p.Arg474Gln Uncertain significance ★ ⚠ same type

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-glu44lys (accessed [today's date]).

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