Is MORC2 p.Lys89Glu (c.265A>G) pathogenic?

MORC2 p.Lys89Glu (c.265A>G) is classified Likely pathogenic in MORC2 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9942); Absent from gnomAD v4.1; Associated with developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy.

What condition is associated with MORC2 p.Lys89Glu (c.265A>G)?

MORC2 p.Lys89Glu (c.265A>G) is associated with developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (ClinVar).

How common is MORC2 p.Lys89Glu (c.265A>G) in the general population?

MORC2 p.Lys89Glu (c.265A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MORC2 p.Lys89Glu (c.265A>G)?

AlphaMissense predicts likely pathogenic (score 0.9942) — an in-silico prediction, not a clinical call.

MORC2 p.Lys89Glu

c.265A>G · VCV3602632

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9942 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy

Computational evidence

Protein change
AlphaMissense	0.9942	likely pathogenic ✓ concordant with ClinVar · top 7% in MORC2
REVEL	0.866	moderately pathogenic-leaning
SaProt	LLR -16.35	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 3,366 bp · p 2.1e-05 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

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: MORC2
Protein: p.Lys89Glu
Coding: c.265A>G
MANE Select: NM_001303256
Type: single nucleotide variant
Location: chr22:30949804 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 9 PDB
Residue 89: a binding site

Full MORC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MORC2 p.Arg132Cys Pathogenic/Likely pathogenic ★★ same condition
MORC2 p.Arg132His Pathogenic/Likely pathogenic ★★ ⚠ same condition
MORC2 p.Arg252Trp Pathogenic/Likely pathogenic ★★ same condition
MORC2 p.Arg266Ser Pathogenic/Likely pathogenic ★★ same condition
MORC2 p.Glu27Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
MORC2 p.Ser87Leu Pathogenic ★★ same condition
MORC2 p.Thr24Ile Pathogenic/Likely pathogenic ★★ same condition
MORC2 p.Thr424Ala Pathogenic/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/morc2-p-lys89glu (accessed [today's date]).

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