Is MORC2 p.Ser388Arg (c.1164C>G) pathogenic?

MORC2 p.Ser388Arg (c.1164C>G) is classified Likely pathogenic in MORC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-14). AlphaMissense: likely pathogenic (0.9906); Absent from gnomAD v4.1.

How common is MORC2 p.Ser388Arg (c.1164C>G) in the general population?

MORC2 p.Ser388Arg (c.1164C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MORC2 p.Ser388Arg (c.1164C>G)?

AlphaMissense predicts likely pathogenic (score 0.9906) — an in-silico prediction, not a clinical call.

MORC2 p.Ser388Arg

c.1164C>G · rs1602485958 · VCV804304

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9906 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9906	likely pathogenic ✓ concordant with ClinVar · top 9% in MORC2
REVEL	0.283	benign-leaning
SaProt	LLR -13.39	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP -1.1, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 270 bp · p 7e-12 · regional, not allelic
Overall
CADD	21.0	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.Ser388Arg
Coding: c.1164C>G
MANE Select: NM_001303256
dbSNP: rs1602485958
Type: single nucleotide variant
Location: chr22:30938115 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 9 PDB
Residue 388: a UniProt-annotated variant site (in digfan)

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

Similar variants

MORC2 p.Ser388Ile Uncertain significance ★★ ⚠ same residue
MORC2 p.Arg132Cys Pathogenic/Likely pathogenic ★★ same type
MORC2 p.Arg132His Pathogenic/Likely pathogenic ★★ ⚠ same type
MORC2 p.Arg252Trp Pathogenic/Likely pathogenic ★★ same type
MORC2 p.Arg266Ser Pathogenic/Likely pathogenic ★★ same type
MORC2 p.Asp466Asn Pathogenic/Likely pathogenic ★★ ⚠ same type
MORC2 p.Glu236Gly Pathogenic/Likely pathogenic ★★ same type
MORC2 p.Glu27Lys Pathogenic/Likely pathogenic ★★ ⚠ 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/morc2-p-ser388arg (accessed [today's date]).

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