Is MAPK8IP3 p.Ser818= (c.2454C>T) pathogenic?

MAPK8IP3 p.Ser818= (c.2454C>T) is classified Benign in MAPK8IP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-18). Low-frequency (popmax 1.66%, afr); Associated with MAPK8IP3-related disorder.

What condition is associated with MAPK8IP3 p.Ser818= (c.2454C>T)?

MAPK8IP3 p.Ser818= (c.2454C>T) is associated with MAPK8IP3-related disorder (ClinVar).

How common is MAPK8IP3 p.Ser818= (c.2454C>T) in the general population?

MAPK8IP3 p.Ser818= (c.2454C>T) is low-frequency (popmax 1.66%, afr) (gnomAD).

MAPK8IP3 p.Ser818=

c.2454C>T · rs115323198 · VCV3045440

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.66%, 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	all four deltas below 0.2 · C>G here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.7	GERP -4.1
Overall
CADD	1.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.66% African / African-American · 1,248/75,024 alleles

Filtering AF 1.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.56%

Overall 0.093% 1,498/1,610,898 alleles · low-frequency exomes 738/1,458,582 · genomes 760/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.66%	60
Admixed American	0.15%	665
East Asian	0.143%	701
Remaining individualsnot grpmax-eligible	0.107%	931
Middle Eastern	0.033%	3,026
South Asian	0.00661%	15,139
European (non-Finnish)	0.00178%	56,138

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.Ser818=
Coding: c.2454C>T
MANE Select: NM_001318852
dbSNP: rs115323198
Type: single nucleotide variant
Location: chr16:1765967 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.19 · 5 PDB
Residue 818: a UniProt-annotated variant site (in nedba)

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-ser818 (accessed [today's date]).

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