Is MAPK1 p.Ile103Val (c.307A>G) pathogenic?

MAPK1 p.Ile103Val (c.307A>G) is classified Uncertain significance in MAPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-30). AlphaMissense: ambiguous (0.5408); Absent from gnomAD v4.1.

How common is MAPK1 p.Ile103Val (c.307A>G) in the general population?

MAPK1 p.Ile103Val (c.307A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPK1 p.Ile103Val (c.307A>G)?

AlphaMissense predicts ambiguous (score 0.5408) — an in-silico prediction, not a clinical call.

MAPK1 p.Ile103Val

c.307A>G · rs2517495481 · VCV2582179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5408 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5408	ambiguous
REVEL	0.165	moderately benign-leaning
SaProt	LLR -8.16	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 1,673 bp · p 0.32 · regional, not allelic
Overall
CADD	24.0	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: MAPK1
Protein: p.Ile103Val
Coding: c.307A>G
MANE Select: NM_002745
dbSNP: rs2517495481
Type: single nucleotide variant
Location: chr22:21806035 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 157 PDB
Residue 103: the protein kinase domain; a β-strand

Full MAPK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK1 p.Ala174Val Pathogenic ★★ ⚠ same type
MAPK1 p.Arg135Thr Likely pathogenic ★★ same type
MAPK1 p.Asp318Asn Pathogenic/Likely pathogenic ★★ same type
MAPK1 p.Asp318Gly Pathogenic ★★ same type
MAPK1 p.Glu322Gln Pathogenic/Likely pathogenic ★★ same type
MAPK1 p.His80Tyr Pathogenic ★★ same type
MAPK1 p.Asn27Asp Uncertain significance ★★ ⚠ same type
MAPK1 p.Ala325= Likely benign ★★ 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/mapk1-p-ile103val (accessed [today's date]).

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