Is MAP3K14 p.Pro565Arg (c.1694C>G) pathogenic?

MAP3K14 p.Pro565Arg (c.1694C>G) is classified Pathogenic in MAP3K14 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-25). AlphaMissense: likely pathogenic (0.9706); Absent from gnomAD v4.1; Associated with immunodeficiency 112.

What condition is associated with MAP3K14 p.Pro565Arg (c.1694C>G)?

MAP3K14 p.Pro565Arg (c.1694C>G) is associated with immunodeficiency 112 (ClinVar).

How common is MAP3K14 p.Pro565Arg (c.1694C>G) in the general population?

MAP3K14 p.Pro565Arg (c.1694C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K14 p.Pro565Arg (c.1694C>G)?

AlphaMissense predicts likely pathogenic (score 0.9706) — an in-silico prediction, not a clinical call.

MAP3K14 p.Pro565Arg

c.1694C>G · rs773929665 · VCV3233307

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9706 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 112

Computational evidence

Protein change
AlphaMissense	0.9706	likely pathogenic ✓ concordant with ClinVar · top 5% in MAP3K14
REVEL	0.806	moderately pathogenic-leaning
SaProt	LLR -14.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 19 kb · p 2.1e-18 · regional, not allelic
Overall
CADD	28.7	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

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.Pro565Arg
Coding: c.1694C>G
MANE Select: NM_003954
dbSNP: rs773929665
Type: single nucleotide variant
Location: chr17:45271185 (GRCh38)
Gene constraint: LOEUF 0.263 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.00 · 8 PDB
Residue 565: the protein kinase domain; a UniProt-annotated variant site (in imd112; likely pathogenic; loss of function in non-canonical nf-kappab signal transduction; unable to phosphorylate chuk/ikka); the 'interaction with zfp91' region; an α-helix

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

Disease context

immunodeficiency 112 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP3K14 p.Pro565= Likely benign ★ same residue
MAP3K14 p.Val345Met Uncertain significance ★ ⚠ same condition
MAP3K14 p.Ala103Thr Uncertain significance ★★ ⚠ same type
MAP3K14 p.Ala142Ser Uncertain significance ★★ ⚠ same type
MAP3K14 p.Ala575Thr Uncertain significance ★★ ⚠ same type
MAP3K14 p.Arg131His Uncertain significance ★★ ⚠ same type
MAP3K14 p.Arg146Gln Uncertain significance ★★ ⚠ same type
MAP3K14 p.Arg218Gln 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/map3k14-p-pro565arg (accessed [today's date]).

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