Is MAP2K2 p.Asp285= (c.855C>T) pathogenic?

MAP2K2 p.Asp285= (c.855C>T) is classified Likely benign in MAP2K2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). Very rare (popmax 0.00225%, eas); Associated with RASopathy.

What condition is associated with MAP2K2 p.Asp285= (c.855C>T)?

MAP2K2 p.Asp285= (c.855C>T) is associated with RASopathy (ClinVar).

How common is MAP2K2 p.Asp285= (c.855C>T) in the general population?

MAP2K2 p.Asp285= (c.855C>T) is very rare (popmax 0.00225%, eas) (gnomAD).

MAP2K2 p.Asp285=

c.855C>T · rs778350557 · VCV2740675

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00225%, eas)

Conditions

RASopathy

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 -1.9	GERP -3.9
Overall
CADD	5.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00225% East Asian · 1/44,536 alleles

Filtering AF 0.000502% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000997% 16/1,605,354 alleles · very rare exomes 14/1,453,220 · genomes 2/152,134 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00225%	44,536
Admixed American	0.0017%	58,910
Remaining individualsnot grpmax-eligible	0.00161%	62,126
Finnishnot grpmax-eligible	0.00161%	62,144
South Asian	0.00111%	89,910
European (non-Finnish)	0.000935%	106,959

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: MAP2K2
Protein: p.Asp285=
Coding: c.855C>T
MANE Select: NM_030662
dbSNP: rs778350557
Type: single nucleotide variant
Location: chr19:4099265 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB
Residue 285: the protein kinase domain

Full MAP2K2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RASopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP2K2 p.Asp285Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
MAP2K2 p.Asp285His Uncertain significance ★ ⚠ same residue
MAP2K2 p.Asp285Val Uncertain significance ★ ⚠ same residue
MAP2K2 p.Glu207Lys Likely pathogenic ★★★ same condition
MAP2K2 p.Phe57Cys Pathogenic ★★★ same condition
MAP2K2 p.Pro128Gln Pathogenic ★★★ same condition
MAP2K2 p.Tyr134Cys Likely pathogenic ★★★ same condition
MAP2K2 p.Tyr134His 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/map2k2-p-asp285 (accessed [today's date]).

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