Is MAPK8IP3 p.Ser256= (c.768C>T) pathogenic?

MAPK8IP3 p.Ser256= (c.768C>T) is classified Benign in MAPK8IP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-12). Common (popmax 11.3%, mid) — too common for a highly-penetrant pathogenic allele; Associated with MAPK8IP3-related disorder.

What condition is associated with MAPK8IP3 p.Ser256= (c.768C>T)?

MAPK8IP3 p.Ser256= (c.768C>T) is associated with MAPK8IP3-related disorder (ClinVar).

MAPK8IP3 p.Ser256=

Q: How common is MAPK8IP3 p.Ser256= (c.768C>T) in the general population?

MAPK8IP3 p.Ser256= (c.768C>T) is common (popmax 11.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.768C>T · rs2294613 · VCV3059557

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 11.3%, mid) — too common for a highly-penetrant pathogenic allele

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 -7.2	GERP -4.5
Overall
CADD	6.248	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.3% Middle Eastern · 687/6,060 alleles

Filtering AF 10.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.4%

Overall 9.71% 156,655/1,613,412 alleles · common exomes 142,741/1,461,166 · genomes 13,914/152,246 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	11.3%	9
Ashkenazi Jewishnot grpmax-eligible	10.8%	9
European (non-Finnish)	10.2%	10
South Asian	9.74%	10
African / African-American	9.65%	10
Remaining individualsnot grpmax-eligible	9.42%	11
Finnishnot grpmax-eligible	8.41%	12
East Asian	6.84%	15
Amishnot grpmax-eligible	5.37%	19
Admixed American	3.94%	25

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.Ser256=
Coding: c.768C>T
MANE Select: NM_001318852
dbSNP: rs2294613
Type: single nucleotide variant
Location: chr16:1747049 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.19 · 5 PDB
Residue 256: 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-ser256 (accessed [today's date]).

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