Is MORC2 p.Ser87Pro (c.259T>C) pathogenic?

MORC2 p.Ser87Pro (c.259T>C) is classified Pathogenic in MORC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: likely pathogenic (0.9812); Absent from gnomAD v4.1; Associated with developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy.

What condition is associated with MORC2 p.Ser87Pro (c.259T>C)?

MORC2 p.Ser87Pro (c.259T>C) is associated with developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (ClinVar).

How common is MORC2 p.Ser87Pro (c.259T>C) in the general population?

MORC2 p.Ser87Pro (c.259T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MORC2 p.Ser87Pro (c.259T>C)?

AlphaMissense predicts likely pathogenic (score 0.9812) — an in-silico prediction, not a clinical call.

MORC2 p.Ser87Pro

c.259T>C · rs2147284796 · VCV1699240

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9812 · 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	0.9812	likely pathogenic ✓ concordant with ClinVar
REVEL	0.863	moderately pathogenic-leaning
SaProt	LLR -10.85	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 11	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	28.7	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.Ser87Pro
Coding: c.259T>C
MANE Select: NM_001303256
dbSNP: rs2147284796
Type: single nucleotide variant
Location: chr22:30949810 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 9 PDB
Residue 87: a binding site; a UniProt-annotated variant site (in cmt2z and digfan; decreased atpase activity; atp-independent homodimerization; increases hush-dependent gene silencing)

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.Ser87Leu Pathogenic ★★ same residue
MORC2 p.Ser87= Likely benign ★ same residue
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.Thr24Ile 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-ser87pro (accessed [today's date]).

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