Is MAPK8IP3 p.Cys856Ser (c.2566T>A) pathogenic?

MAPK8IP3 p.Cys856Ser (c.2566T>A) is classified Uncertain significance in MAPK8IP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-11). AlphaMissense: likely pathogenic (0.7514); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MAPK8IP3 p.Cys856Ser (c.2566T>A)?

MAPK8IP3 p.Cys856Ser (c.2566T>A) is associated with Inborn genetic diseases (ClinVar).

How common is MAPK8IP3 p.Cys856Ser (c.2566T>A) in the general population?

MAPK8IP3 p.Cys856Ser (c.2566T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPK8IP3 p.Cys856Ser (c.2566T>A)?

AlphaMissense predicts likely pathogenic (score 0.7514) — an in-silico prediction, not a clinical call.

MAPK8IP3 p.Cys856Ser

c.2566T>A · rs2548109222 · VCV2288751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7514 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7514	likely pathogenic
REVEL	0.281	benign-leaning
SaProt	LLR -3.52	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 5,099 bp · p 0.00099 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM C855S vs ClinVar C856S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAPK8IP3
Protein: p.Cys856Ser
Coding: c.2566T>A
MANE Select: NM_001318852
dbSNP: rs2548109222
Type: single nucleotide variant
Location: chr16:1766079 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.19 · 5 PDB
Residue 856: a UniProt-annotated variant site (in nedba)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAPK8IP3 p.Arg579Cys Pathogenic/Likely pathogenic ★★ same condition
MAPK8IP3 c.1898+5G>A Uncertain significance ★★ same condition
MAPK8IP3 p.Ala883Thr Uncertain significance ★★ ⚠ same condition
MAPK8IP3 p.Arg1012Cys Uncertain significance ★★ ⚠ same condition
MAPK8IP3 p.Arg1187Gln Uncertain significance ★★ ⚠ same condition
MAPK8IP3 p.Arg308Cys Uncertain significance ★★ ⚠ same condition
MAPK8IP3 p.Arg310Trp Uncertain significance ★★ ⚠ same condition
MAPK8IP3 p.Arg612Cys 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-cys856ser (accessed [today's date]).

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