Is MAP3K13 p.Arg548Trp (c.1642C>T) pathogenic?

MAP3K13 p.Arg548Trp (c.1642C>T) is classified Uncertain significance in MAP3K13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: ambiguous (0.5613); Very rare (popmax 0.00333%, amr).

How common is MAP3K13 p.Arg548Trp (c.1642C>T) in the general population?

MAP3K13 p.Arg548Trp (c.1642C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about MAP3K13 p.Arg548Trp (c.1642C>T)?

AlphaMissense predicts ambiguous (score 0.5613) — an in-silico prediction, not a clinical call.

MAP3K13 p.Arg548Trp

c.1642C>T · VCV4549398

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5613	ambiguous
REVEL	0.212	benign-leaning
SaProt	LLR -8.66	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 2.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 32 kb · p 1.3e-08 · regional, not allelic
Overall
CADD	32.0	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 0.00333% Admixed American · 2/59,996 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00112% 18/1,613,810 alleles · very rare exomes 16/1,461,632 · genomes 2/152,178 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,998
East Asian	0.00223%	44,896
South Asian	0.0022%	45,539
European (non-Finnish)	0.0011%	90,758

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.Arg548Trp
Coding: c.1642C>T
MANE Select: NM_004721
Type: single nucleotide variant
Location: chr3:185466962 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.92
Residue 548: the 'disordered' region

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

Similar variants

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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-arg548trp (accessed [today's date]).

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