Is MARK2 p.Arg71Ter (c.211C>T) pathogenic?

MARK2 p.Arg71Ter (c.211C>T) is classified Conflicting classifications of pathogenicity in MARK2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-06-03). Very rare (popmax 6.2e-05%); Associated with intellectual developmental disorder, autosomal dominant 76.

What condition is associated with MARK2 p.Arg71Ter (c.211C>T)?

MARK2 p.Arg71Ter (c.211C>T) is associated with intellectual developmental disorder, autosomal dominant 76, intellectual disability, autism spectrum disorder (ClinVar).

How common is MARK2 p.Arg71Ter (c.211C>T) in the general population?

MARK2 p.Arg71Ter (c.211C>T) is very rare (popmax 6.2e-05%) (gnomAD).

MARK2 p.Arg71Ter

c.211C>T · rs868032104 · VCV3253624

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

intellectual developmental disorder, autosomal dominant 76

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 0.87, phastCons 1
Overall
CADD	38.0	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

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,892 alleles · very rare exomes 1/1,461,750 · genomes 0/152,142 · joint denominator

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: MARK2
Protein: p.Arg71Ter
Coding: c.211C>T
MANE Select: NM_001039469
dbSNP: rs868032104
Type: single nucleotide variant
Location: chr11:63895315 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.21 · 5 PDB
Residue 71: the protein kinase domain; a UniProt-annotated variant site (in mrd76; likely pathogenic); a β-strand

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

Disease context

intellectual developmental disorder, autosomal dominant 76 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability autism spectrum disorder

Similar variants

MARK2 p.Ala432Thr Uncertain significance ★★ ⚠ same condition
MARK2 c.1934+1G>A Likely pathogenic ★ same condition
MARK2 c.2006+2T>G 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 c.1101+5G>A Uncertain significance ★ same condition
MARK2 p.Arg302Ter Uncertain significance ★ 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-arg71ter (accessed [today's date]).

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