Is MAP3K13 p.Arg503Cys (c.1507C>T) pathogenic?

MAP3K13 p.Arg503Cys (c.1507C>T) is classified Uncertain significance in MAP3K13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely pathogenic (0.9195); Ultra-rare (popmax 0.0329%, mid).

How common is MAP3K13 p.Arg503Cys (c.1507C>T) in the general population?

MAP3K13 p.Arg503Cys (c.1507C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about MAP3K13 p.Arg503Cys (c.1507C>T)?

AlphaMissense predicts likely pathogenic (score 0.9195) — an in-silico prediction, not a clinical call.

MAP3K13 p.Arg503Cys

c.1507C>T · rs151275315 · VCV2508471

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9195 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9195	likely pathogenic
REVEL	0.32	indeterminate
SaProt	LLR -12.67	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 32 kb · p 1.3e-08 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,076 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000868% 14/1,613,784 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,038
Admixed American	0.005%	19,995
Remaining individualsnot grpmax-eligible	0.0048%	20,823
African / African-American	0.00134%	74,888
European (non-Finnish)	0.000424%	235,970

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.Arg503Cys
Coding: c.1507C>T
MANE Select: NM_004721
dbSNP: rs151275315
Type: single nucleotide variant
Location: chr3:185466827 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.92
Residue 503: the 'leucine-zipper 2' region

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-arg503cys (accessed [today's date]).

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