Is MAPK8IP3 p.Pro824= (c.2472C>T) pathogenic?

MAPK8IP3 p.Pro824= (c.2472C>T) is classified Likely benign in MAPK8IP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-01). Rare (popmax 0.118%, eas).

How common is MAPK8IP3 p.Pro824= (c.2472C>T) in the general population?

MAPK8IP3 p.Pro824= (c.2472C>T) is rare (popmax 0.118%, eas) (gnomAD).

MAPK8IP3 p.Pro824=

c.2472C>T · rs200111591 · VCV1694772

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.118%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.2	GERP -4.1
Overall
CADD	0.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.118% East Asian · 53/44,872 alleles

Filtering AF 0.0927% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0836%

Overall 0.0328% 529/1,612,508 alleles · rare exomes 444/1,460,176 · genomes 85/152,332 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.149%	672
East Asiangrpmax	0.118%	847
Remaining individualsnot grpmax-eligible	0.0849%	1,178
African / African-American	0.0826%	1,210
European (non-Finnish)	0.0244%	4,097
South Asian	0.0176%	5,689
Middle Eastern	0.0165%	6,058
Admixed American	0.0133%	7,497
Finnishnot grpmax-eligible	0.00637%	15,692

Ashkenazi Jewish 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.Pro824=
Coding: c.2472C>T
MANE Select: NM_001318852
dbSNP: rs200111591
Type: single nucleotide variant
Location: chr16:1765985 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.19 · 5 PDB
Residue 824: 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-pro824 (accessed [today's date]).

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