Is MAPK1 p.Ala52Asp (c.155C>A) pathogenic?

MAPK1 p.Ala52Asp (c.155C>A) is classified Uncertain significance in MAPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Noonan syndrome 13.

What condition is associated with MAPK1 p.Ala52Asp (c.155C>A)?

MAPK1 p.Ala52Asp (c.155C>A) is associated with Noonan syndrome 13 (ClinVar).

How common is MAPK1 p.Ala52Asp (c.155C>A) in the general population?

MAPK1 p.Ala52Asp (c.155C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPK1 p.Ala52Asp (c.155C>A)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

MAPK1 p.Ala52Asp

c.155C>A · rs2145705712 · VCV1699351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Noonan syndrome 13

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 4% in MAPK1
REVEL	0.825	moderately pathogenic-leaning
SaProt	LLR -15.69	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 60 kb · p 0.89 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Ala52Asp
Coding: c.155C>A
MANE Select: NM_002745
dbSNP: rs2145705712
Type: single nucleotide variant
Location: chr22:21807811 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 157 PDB
Residue 52: the protein kinase domain; a β-strand

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

Disease context

Noonan syndrome 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAPK1 p.Ala174Val Pathogenic ★★ ⚠ same condition
MAPK1 p.Asp318Asn Pathogenic/Likely pathogenic ★★ same condition
MAPK1 p.Asp318Gly Pathogenic ★★ same condition
MAPK1 p.Glu322Gln Pathogenic/Likely pathogenic ★★ same condition
MAPK1 p.His80Tyr Pathogenic ★★ same condition
MAPK1 p.Asn82Asp Likely pathogenic ★ same condition
MAPK1 p.Ile74Asn Pathogenic ★ same condition
MAPK1 p.Tyr316His Likely pathogenic ★ 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/mapk1-p-ala52asp (accessed [today's date]).

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