Is MAP3K14 p.Lys607= (c.1821G>A) pathogenic?

MAP3K14 p.Lys607= (c.1821G>A) is classified Uncertain significance in MAP3K14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). Absent from gnomAD v4.1; Associated with NIK deficiency.

What condition is associated with MAP3K14 p.Lys607= (c.1821G>A)?

MAP3K14 p.Lys607= (c.1821G>A) is associated with NIK deficiency (ClinVar).

How common is MAP3K14 p.Lys607= (c.1821G>A) in the general population?

MAP3K14 p.Lys607= (c.1821G>A) is absent from gnomAD v4.1 (gnomAD).

How is NIK deficiency inherited?

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

MAP3K14 p.Lys607=

c.1821G>A · rs2508982285 · VCV2121097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

NIK deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.84	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.77	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Overall
CADD	19.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAP3K14
Protein: p.Lys607=
Coding: c.1821G>A
MANE Select: NM_003954
dbSNP: rs2508982285
Type: single nucleotide variant
Location: chr17:45271058 (GRCh38)
Gene constraint: LOEUF 0.263 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.00 · 8 PDB
Residue 607: the protein kinase domain; the 'interaction with zfp91' region; an α-helix

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.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
MAP3K14 p.Arg99His 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-lys607 (accessed [today's date]).

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