Is MARK2 p.Arg482Ter (c.1444C>T) pathogenic?

MARK2 p.Arg482Ter (c.1444C>T) is classified Uncertain significance in MARK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-22). Very rare (popmax 0.000169%, nfe); Associated with Paediatric disorders.

What condition is associated with MARK2 p.Arg482Ter (c.1444C>T)?

MARK2 p.Arg482Ter (c.1444C>T) is associated with Paediatric disorders (ClinVar).

How common is MARK2 p.Arg482Ter (c.1444C>T) in the general population?

MARK2 p.Arg482Ter (c.1444C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

MARK2 p.Arg482Ter

c.1444C>T · VCV4820615

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Paediatric disorders

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 14 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.68, phastCons 0.98
Overall
CADD	36.0	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 0.000169% European (non-Finnish) · 2/1,179,998 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,066 alleles · very rare exomes 3/1,461,758 · genomes 0/152,308 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)grpmax	0.000169%	589,998

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg482Ter
Coding: c.1444C>T
MANE Select: NM_001039469
Type: single nucleotide variant
Location: chr11:63903088 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.21 · 5 PDB
Residue 482: 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

Paediatric disorders

Similar variants

MARK2 c.1934+1G>A Likely pathogenic ★ same condition
MARK2 p.Gln222fs Pathogenic ★ same condition
MARK2 p.Tyr267Ter Pathogenic ★ same condition
MARK2 p.Ala432Thr Uncertain significance ★★ ⚠ same type
MARK2 p.Arg264Ser Uncertain significance ★★ ⚠ same type
MARK2 c.337+8C>G Likely benign ★★ same type
MARK2 p.Pro459= Benign ★★ same type
MARK2 p.Pro740= Benign ★★ same type

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-arg482ter (accessed [today's date]).

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