Is MARK2 p.Ala630fs (c.1888dup) pathogenic?

MARK2 p.Ala630fs (c.1888dup) is classified Uncertain significance in MARK2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-12-12). No allele count reported in gnomAD v4.1 (AN 1,611,876); Associated with autism spectrum disorder.

What condition is associated with MARK2 p.Ala630fs (c.1888dup)?

MARK2 p.Ala630fs (c.1888dup) is associated with autism spectrum disorder (ClinVar).

How common is MARK2 p.Ala630fs (c.1888dup) in the general population?

MARK2 p.Ala630fs (c.1888dup) is no allele count reported in gnomAD v4.1 (AN 1,611,876) (gnomAD).

MARK2 p.Ala630fs

c.1888dup · rs2539335876 · VCV3253635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,876)

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 16 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 0.88, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,876). 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.Ala630fs
Coding: c.1888dup
MANE Select: NM_001039469
dbSNP: rs2539335876
Type: Duplication
Location: chr11:63904991 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.21 · 5 PDB
Residue 630: 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.Leu506fs Likely pathogenic same condition
MARK2 p.Leu97fs Pathogenic same condition
MARK2 p.Thr87fs Likely pathogenic same condition
MARK2 p.Val395fs 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
MARK2 p.Gly135Arg 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/mark2-p-ala630fs (accessed [today's date]).

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