Is MARK2 p.Gln253Ter (c.757C>T) pathogenic?

MARK2 p.Gln253Ter (c.757C>T) is classified Pathogenic in MARK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-03). Absent from gnomAD v4.1; Associated with autism spectrum disorder.

What condition is associated with MARK2 p.Gln253Ter (c.757C>T)?

MARK2 p.Gln253Ter (c.757C>T) is associated with autism spectrum disorder (ClinVar).

How common is MARK2 p.Gln253Ter (c.757C>T) in the general population?

MARK2 p.Gln253Ter (c.757C>T) is absent from gnomAD v4.1 (gnomAD).

MARK2 p.Gln253Ter

c.757C>T · rs2539319606 · VCV3253648

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autism spectrum disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 8 of 19
Splicing
SpliceAI	Δ0.51	donor gain · deltas
Pangolin	Δ0.42	loss · gain 0.35 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Overall
CADD	47.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: MARK2
Protein: p.Gln253Ter
Coding: c.757C>T
MANE Select: NM_001039469
dbSNP: rs2539319606
Type: single nucleotide variant
Location: chr11:63900099 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.21 · 5 PDB
Residue 253: the protein kinase domain; a UniProt-annotated variant site (in mrd76; likely pathogenic); a UniProt-annotated variant site (in mrd76; pathogenic)

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 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
MARK2 p.Arg302Ter Uncertain significance ★ same condition
MARK2 p.Arg71Ter Conflicting classifications of pathogenicity ★ ⚠ same condition
MARK2 p.Phe194Ser Uncertain significance ★ ⚠ same condition
MARK2 c.1101+1G>A 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-gln253ter (accessed [today's date]).

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