Is MAP3K14 p.Arg601= (c.1803A>G) pathogenic?

MAP3K14 p.Arg601= (c.1803A>G) is classified Likely benign in MAP3K14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-11). Rare (popmax 0.103%, eas); Associated with NIK deficiency.

What condition is associated with MAP3K14 p.Arg601= (c.1803A>G)?

MAP3K14 p.Arg601= (c.1803A>G) is associated with NIK deficiency (ClinVar).

How common is MAP3K14 p.Arg601= (c.1803A>G) in the general population?

MAP3K14 p.Arg601= (c.1803A>G) is rare (popmax 0.103%, eas) (gnomAD).

How is NIK deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MAP3K14 p.Arg601=

c.1803A>G · rs371145129 · VCV1151371

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.103%, eas)

Conditions

NIK deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.1	GERP -3.2, phastCons 0.001
Overall
CADD	6.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.103% East Asian · 46/44,862 alleles

Filtering AF 0.0789% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0707%

Overall 0.00539% 87/1,613,028 alleles · rare exomes 72/1,460,750 · genomes 15/152,278 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.103%	975
South Asian	0.0253%	3,959
Remaining individualsnot grpmax-eligible	0.0224%	4,462
Admixed American	0.00167%	59,888
European (non-Finnish)	0.000254%	393,236

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: MAP3K14
Protein: p.Arg601=
Coding: c.1803A>G
MANE Select: NM_003954
dbSNP: rs371145129
Type: single nucleotide variant
Location: chr17:45271076 (GRCh38)
Gene constraint: LOEUF 0.263 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.00 · 8 PDB
Residue 601: the protein kinase domain; the 'interaction with zfp91' region

Full MAP3K14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NIK deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For NIK deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

MAP3K14 p.Arg601Gln Uncertain significance ★ ⚠ same residue
MAP3K14 p.Ala103Thr Uncertain significance ★★ ⚠ same condition
MAP3K14 p.Ala142Ser Uncertain significance ★★ ⚠ same condition
MAP3K14 p.Ala575Thr Uncertain significance ★★ ⚠ same condition
MAP3K14 p.Arg131His Uncertain significance ★★ ⚠ same condition
MAP3K14 p.Arg146Gln Uncertain significance ★★ ⚠ same condition
MAP3K14 p.Arg218Gln Uncertain significance ★★ ⚠ same condition
MAP3K14 p.Arg432Trp Uncertain significance ★★ ⚠ same condition

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/map3k14-p-arg601 (accessed [today's date]).

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