Is MAPK8IP3 p.Ser71Arg (c.213C>A) pathogenic?

MAPK8IP3 p.Ser71Arg (c.213C>A) is classified Uncertain significance in MAPK8IP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely pathogenic (0.7649); Absent from gnomAD v4.1.

How common is MAPK8IP3 p.Ser71Arg (c.213C>A) in the general population?

MAPK8IP3 p.Ser71Arg (c.213C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPK8IP3 p.Ser71Arg (c.213C>A)?

AlphaMissense predicts likely pathogenic (score 0.7649) — an in-silico prediction, not a clinical call.

MAPK8IP3 p.Ser71Arg

c.213C>A · rs2037396946 · VCV2502112

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7649 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7649	likely pathogenic
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.53	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 2.1	GERP -2.5, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 18 kb · p 2.8e-14 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

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

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.Ser71Arg
Coding: c.213C>A
MANE Select: NM_001318852
dbSNP: rs2037396946
Type: single nucleotide variant
Location: chr16:1706552 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.19 · 5 PDB
Residue 71: the rh1 domain; a UniProt-annotated variant site (in nedba); the 'kinesin-binding domain (kbd); essential for its function in axon elongation' region

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-ser71arg (accessed [today's date]).

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