Is MAPK8IP3 p.Ser280= (c.840C>T) pathogenic?

MAPK8IP3 p.Ser280= (c.840C>T) is classified Likely benign in MAPK8IP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-05). Very rare (popmax 0.00223%, eas).

How common is MAPK8IP3 p.Ser280= (c.840C>T) in the general population?

MAPK8IP3 p.Ser280= (c.840C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

MAPK8IP3 p.Ser280=

c.840C>T · VCV4927324

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -11	GERP -4.5
Overall
CADD	4.841	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000372% 6/1,613,976 alleles · very rare exomes 6/1,461,612 · genomes 0/152,364 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00313%	31,943
East Asiangrpmax	0.00223%	44,880
European (non-Finnish)	0.000254%	393,317

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser280=
Coding: c.840C>T
MANE Select: NM_001318852
Type: single nucleotide variant
Location: chr16:1747121 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.19 · 5 PDB
Residue 280: a UniProt-annotated variant site (in nedba); the 'disordered' region

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

Similar variants

MAPK8IP3 p.Arg1147Cys Pathogenic/Likely pathogenic ★★ same type
MAPK8IP3 p.Arg579Cys Pathogenic/Likely pathogenic ★★ same type
MAPK8IP3 p.Gln468Ter Pathogenic/Likely pathogenic ★★ same type
MAPK8IP3 p.Glu27Ter Likely pathogenic ★★ same type
MAPK8IP3 p.Glu462Gly Likely pathogenic ★★ same type
MAPK8IP3 p.Leu445Pro Likely pathogenic ★★ same type
MAPK8IP3 p.Tyr37Ter Likely pathogenic ★★ same type
MAPK8IP3 c.1898+5G>A 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/mapk8ip3-p-ser280 (accessed [today's date]).

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