Is MAPK8IP3 p.Asp216= (c.648C>T) pathogenic?

MAPK8IP3 p.Asp216= (c.648C>T) is classified Likely benign in MAPK8IP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-12-22). Ultra-rare (popmax 0.0831%, afr); Associated with MAPK8IP3-related disorder.

What condition is associated with MAPK8IP3 p.Asp216= (c.648C>T)?

MAPK8IP3 p.Asp216= (c.648C>T) is associated with MAPK8IP3-related disorder (ClinVar).

How common is MAPK8IP3 p.Asp216= (c.648C>T) in the general population?

MAPK8IP3 p.Asp216= (c.648C>T) is ultra-rare (popmax 0.0831%, afr) (gnomAD).

MAPK8IP3 p.Asp216=

c.648C>T · rs201722762 · VCV3045342

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0831%, afr)

Conditions

MAPK8IP3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.38	GERP -3, phastCons 0.99
Overall
CADD	11.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0831% African / African-American · 60/72,234 alleles

Filtering AF 0.0662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0601%

Overall 0.0066% 104/1,575,838 alleles · ultra-rare exomes 75/1,423,484 · genomes 29/152,354 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0831%	1,204
Remaining individualsnot grpmax-eligible	0.0295%	3,388
South Asian	0.0117%	8,541
Ashkenazi Jewishnot grpmax-eligible	0.00351%	28,522
East Asian	0.00246%	40,590
European (non-Finnish)	0.0012%	83,201

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.Asp216=
Coding: c.648C>T
MANE Select: NM_001318852
dbSNP: rs201722762
Type: single nucleotide variant
Location: chr16:1743377 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.19 · 5 PDB
Residue 216: a UniProt-annotated variant site (in nedba); the 'jnk-binding domain (jbd); essential for its function in axon elongation' region

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

Disease context

MAPK8IP3-related disorder

Similar variants

MAPK8IP3 p.Asp216Asn Uncertain significance ★ ⚠ same residue
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

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-asp216 (accessed [today's date]).

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