Is MAPK8IP3 p.Val1007Met (c.3019G>A) pathogenic?

MAPK8IP3 p.Val1007Met (c.3019G>A) is classified Uncertain significance in MAPK8IP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.8386); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with MAPK8IP3 p.Val1007Met (c.3019G>A)?

MAPK8IP3 p.Val1007Met (c.3019G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MAPK8IP3 p.Val1007Met (c.3019G>A) in the general population?

MAPK8IP3 p.Val1007Met (c.3019G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MAPK8IP3 p.Val1007Met (c.3019G>A)?

AlphaMissense predicts likely pathogenic (score 0.8386) — an in-silico prediction, not a clinical call.

MAPK8IP3 p.Val1007Met

c.3019G>A · VCV4624287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8386 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8386	likely pathogenic
REVEL	0.313	indeterminate
SaProt	LLR -13.07	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.80	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 5,099 bp · p 0.00099 · regional, not allelic
Overall
CADD	28.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V1006M vs ClinVar V1007M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Overall 0.000657% 1/152,250 alleles · very rare

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: MAPK8IP3
Protein: p.Val1007Met
Coding: c.3019G>A
MANE Select: NM_001318852
Type: single nucleotide variant
Location: chr16:1766802 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.19 · 5 PDB
Residue 1007: a UniProt-annotated variant site (in nedba)

Full MAPK8IP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAPK8IP3 p.Val1007= Likely benign ★ same residue
MAPK8IP3 p.Arg579Cys Pathogenic/Likely pathogenic ★★ same condition
MAPK8IP3 c.1898+5G>A Uncertain significance ★★ same condition
MAPK8IP3 p.Ala883Thr Uncertain significance ★★ ⚠ same condition
MAPK8IP3 p.Arg1012Cys Uncertain significance ★★ ⚠ same condition
MAPK8IP3 p.Arg1187Gln Uncertain significance ★★ ⚠ same condition
MAPK8IP3 p.Arg308Cys Uncertain significance ★★ ⚠ same condition
MAPK8IP3 p.Arg310Trp 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/mapk8ip3-p-val1007met (accessed [today's date]).

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