Is MARK2 p.Val395fs (c.1181dup) pathogenic?

MARK2 p.Val395fs (c.1181dup) is classified Pathogenic in MARK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-03). No gnomAD frequency available for this variant; Associated with autism spectrum disorder.

What condition is associated with MARK2 p.Val395fs (c.1181dup)?

MARK2 p.Val395fs (c.1181dup) is associated with autism spectrum disorder (ClinVar).

How common is MARK2 p.Val395fs (c.1181dup) in the general population?

MARK2 p.Val395fs (c.1181dup) is no gnomAD frequency available for this variant (gnomAD).

MARK2 p.Val395fs

c.1181dup · rs2539326870 · VCV3253629

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autism spectrum disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 12 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.43	GERP -0.2, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MARK2
Protein: p.Val395fs
Coding: c.1181dup
MANE Select: NM_001039469
dbSNP: rs2539326870
Type: Duplication
Location: chr11:63902275 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.21 · 5 PDB
Residue 395: a UniProt-annotated variant site (in mrd76; likely pathogenic); a UniProt-annotated variant site (in mrd76; pathogenic); the 'disordered' region

Full MARK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autism spectrum disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MARK2 p.Ala630fs Uncertain significance ★ same condition
MARK2 p.Val395Ala Uncertain significance ★ ⚠ same residue
MARK2 p.Leu506fs Likely pathogenic same condition
MARK2 p.Leu97fs Pathogenic same condition
MARK2 p.Thr87fs Likely pathogenic same condition
MARK2 c.1934+1G>A Likely pathogenic ★ same condition
MARK2 c.337+1G>T Pathogenic ★ same condition
MARK2 p.Arg584Ter 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/mark2-p-val395fs (accessed [today's date]).

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