Is MAP3K13 p.Arg53Gln (c.158G>A) pathogenic?

MAP3K13 p.Arg53Gln (c.158G>A) is classified Likely benign in MAP3K13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). AlphaMissense: likely benign (0.0601); Ultra-rare (popmax 0.0245%, eas).

How common is MAP3K13 p.Arg53Gln (c.158G>A) in the general population?

MAP3K13 p.Arg53Gln (c.158G>A) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about MAP3K13 p.Arg53Gln (c.158G>A)?

AlphaMissense predicts likely benign (score 0.0601) — an in-silico prediction, not a clinical call.

MAP3K13 p.Arg53Gln

c.158G>A · rs35961174 · VCV2598834

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0601 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0601	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -5.69	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 0.16	GERP -2.8
Regional constraint	o/e 0.98	unconstrained · MANE · 381 bp · p 0.77 · regional, not allelic
Overall
CADD	0.735	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 0.0245% East Asian · 11/44,878 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00155% 25/1,614,152 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,080
African / African-American	0.004%	25,017
South Asian	0.0022%	45,537
Admixed American	0.00167%	60,018
European (non-Finnish)	0.000678%	147,504

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.Arg53Gln
Coding: c.158G>A
MANE Select: NM_004721
dbSNP: rs35961174
Type: single nucleotide variant
Location: chr3:185428739 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.92

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

Similar variants

MAP3K13 p.Arg53Gly Uncertain significance ★ ⚠ same residue
MAP3K13 p.Ala416Thr Uncertain significance ★ ⚠ same type
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

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-arg53gln (accessed [today's date]).

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