Is MAPK8IP3 p.Ser1245= (c.3735G>A) pathogenic?

MAPK8IP3 p.Ser1245= (c.3735G>A) is classified Likely benign in MAPK8IP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-01). Ultra-rare (popmax 0.028%, afr).

How common is MAPK8IP3 p.Ser1245= (c.3735G>A) in the general population?

MAPK8IP3 p.Ser1245= (c.3735G>A) is ultra-rare (popmax 0.028%, afr) (gnomAD).

MAPK8IP3 p.Ser1245=

c.3735G>A · VCV4534256

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

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 -20	GERP -5.3
Overall
CADD	0.108	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.028% African / African-American · 21/74,908 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.0239% 382/1,600,284 alleles · ultra-rare exomes 348/1,448,088 · genomes 34/152,196 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0385%	2,596
African / African-Americangrpmax	0.028%	3,567
European (non-Finnish)	0.0273%	3,662
Middle Eastern	0.0165%	6,072
Admixed American	0.0134%	7,489
Ashkenazi Jewishnot grpmax-eligible	0.00678%	14,755
Finnishnot grpmax-eligible	0.00581%	17,211
South Asian	0.0011%	91,014

Remaining individuals 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.Ser1245=
Coding: c.3735G>A
MANE Select: NM_001318852
Type: single nucleotide variant
Location: chr16:1768371 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.19 · 5 PDB
Residue 1245: a UniProt-annotated variant site (in nedba)

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-ser1245 (accessed [today's date]).

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