Is MORC2 p.Ser944Pro (c.2830T>C) pathogenic?

MORC2 p.Ser944Pro (c.2830T>C) is classified Uncertain significance in MORC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-10). AlphaMissense: likely pathogenic (0.6271); Very rare (popmax 0.00223%, eas).

How common is MORC2 p.Ser944Pro (c.2830T>C) in the general population?

MORC2 p.Ser944Pro (c.2830T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MORC2 p.Ser944Pro (c.2830T>C)?

AlphaMissense predicts likely pathogenic (score 0.6271) — an in-silico prediction, not a clinical call.

MORC2 p.Ser944Pro

c.2830T>C · VCV3367718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6271 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6271	likely pathogenic
REVEL	0.131	moderately benign-leaning
SaProt	LLR -10.52	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 2.7	GERP 0.79, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 7,374 bp · p 2e-10 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.00223% East Asian · 1/44,876 alleles

Overall 6.2e-05% 1/1,613,626 alleles · very rare exomes 1/1,461,336 · genomes 0/152,290 · joint denominator

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: MORC2
Protein: p.Ser944Pro
Coding: c.2830T>C
MANE Select: NM_001303256
Type: single nucleotide variant
Location: chr22:30932370 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 9 PDB

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

Similar variants

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
MORC2 p.Ser87Leu 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-ser944pro (accessed [today's date]).

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