Is MARK2 p.Ser577Asn (c.1730G>A) pathogenic?

MARK2 p.Ser577Asn (c.1730G>A) is classified Uncertain significance in MARK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-27). AlphaMissense: likely benign (0.1639); Absent from gnomAD v4.1; Associated with intellectual developmental disorder, autosomal dominant 76.

What condition is associated with MARK2 p.Ser577Asn (c.1730G>A)?

MARK2 p.Ser577Asn (c.1730G>A) is associated with intellectual developmental disorder, autosomal dominant 76 (ClinVar).

How common is MARK2 p.Ser577Asn (c.1730G>A) in the general population?

MARK2 p.Ser577Asn (c.1730G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MARK2 p.Ser577Asn (c.1730G>A)?

AlphaMissense predicts likely benign (score 0.1639) — an in-silico prediction, not a clinical call.

MARK2 p.Ser577Asn

c.1730G>A · VCV4882679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1639 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual developmental disorder, autosomal dominant 76

Computational evidence

Protein change
AlphaMissense	0.1639	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.58, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 8,317 bp · p 7.7e-13 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ser577Asn
Coding: c.1730G>A
MANE Select: NM_001039469
Type: single nucleotide variant
Location: chr11:63904839 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.21 · 5 PDB
Residue 577: 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

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

Similar variants

MARK2 p.Ala432Thr Uncertain significance ★★ ⚠ same condition
MARK2 c.2006+2T>G Likely pathogenic ★ same condition
MARK2 c.337+1G>T 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
MARK2 p.Arg71Ter Conflicting classifications of pathogenicity ★ ⚠ same condition
MARK2 p.Asp410Glu 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-ser577asn (accessed [today's date]).

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