Is MAPK8IP3 p.Ala284= (c.852C>T) pathogenic?

MAPK8IP3 p.Ala284= (c.852C>T) is classified Likely benign in MAPK8IP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-06). Ultra-rare (popmax 0.0866%, afr); Associated with MAPK8IP3-related disorder.

What condition is associated with MAPK8IP3 p.Ala284= (c.852C>T)?

MAPK8IP3 p.Ala284= (c.852C>T) is associated with MAPK8IP3-related disorder (ClinVar).

How common is MAPK8IP3 p.Ala284= (c.852C>T) in the general population?

MAPK8IP3 p.Ala284= (c.852C>T) is ultra-rare (popmax 0.0866%, afr) (gnomAD).

MAPK8IP3 p.Ala284=

c.852C>T · rs188900682 · VCV3057524

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0866%, 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 -8.7	GERP -4.5
Overall
CADD	2.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0866% African / African-American · 65/75,052 alleles

Filtering AF 0.0697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0635%

Overall 0.00595% 96/1,613,982 alleles · ultra-rare exomes 64/1,461,648 · genomes 32/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0866%	1,155
Remaining individualsnot grpmax-eligible	0.0224%	4,464
South Asian	0.00549%	18,218
Admixed American	0.00333%	30,014
East Asian	0.00223%	44,882
European (non-Finnish)	0.000763%	131,109

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.Ala284=
Coding: c.852C>T
MANE Select: NM_001318852
dbSNP: rs188900682
Type: single nucleotide variant
Location: chr16:1747133 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.19 · 5 PDB
Residue 284: a UniProt-annotated variant site (in nedba); the 'disordered' region

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 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
MAPK8IP3 p.Ala1150Val 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-ala284 (accessed [today's date]).

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