Is MAPK8IP3 p.Val714= (c.2142C>T) pathogenic?

MAPK8IP3 p.Val714= (c.2142C>T) is classified Likely benign in MAPK8IP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-02-09). Rare (popmax 0.185%, afr); Associated with MAPK8IP3-related disorder.

What condition is associated with MAPK8IP3 p.Val714= (c.2142C>T)?

MAPK8IP3 p.Val714= (c.2142C>T) is associated with MAPK8IP3-related disorder (ClinVar).

How common is MAPK8IP3 p.Val714= (c.2142C>T) in the general population?

MAPK8IP3 p.Val714= (c.2142C>T) is rare (popmax 0.185%, afr) (gnomAD).

MAPK8IP3 p.Val714=

c.2142C>T · rs370199618 · VCV3046949

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.185%, afr)

Conditions

MAPK8IP3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 2.6, phastCons 1
Overall
CADD	11.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.185% African / African-American · 137/74,174 alleles

Filtering AF 0.159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.15%

Overall 0.00971% 153/1,576,416 alleles · rare exomes 74/1,424,070 · genomes 79/152,346 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.185%	541
Middle Eastern	0.0179%	5,590
Remaining individualsnot grpmax-eligible	0.0115%	8,727
Admixed American	0.00555%	18,021
South Asian	0.00115%	86,944
European (non-Finnish)	0.000344%	290,548

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.Val714=
Coding: c.2142C>T
MANE Select: NM_001318852
dbSNP: rs370199618
Type: single nucleotide variant
Location: chr16:1764321 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.19 · 5 PDB
Residue 714: a UniProt-annotated variant site (in nedba)

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

Disease context

MAPK8IP3-related disorder

Similar variants

MAPK8IP3 p.Tyr37Ter Likely pathogenic ★★ same condition
MAPK8IP3 p.Val714fs Likely pathogenic ★ same residue
MAPK8IP3 c.1098-4A>G Uncertain significance ★ same condition
MAPK8IP3 p.Asn1189Lys Uncertain significance ★ ⚠ same condition
MAPK8IP3 p.Asn1282Lys Uncertain significance ★ ⚠ same condition
MAPK8IP3 p.Asp1058Asn Uncertain significance ★ ⚠ same condition
MAPK8IP3 p.Met25Ile Uncertain significance ★ ⚠ same condition
MAPK8IP3 p.Ser820Asn 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-val714 (accessed [today's date]).

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