Is MORC2 p.Val413Phe (c.1237G>T) pathogenic?

MORC2 p.Val413Phe (c.1237G>T) is classified Likely pathogenic in MORC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-17). AlphaMissense: ambiguous (0.408); Absent from gnomAD v4.1.

How common is MORC2 p.Val413Phe (c.1237G>T) in the general population?

MORC2 p.Val413Phe (c.1237G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MORC2 p.Val413Phe (c.1237G>T)?

AlphaMissense predicts ambiguous (score 0.408) — an in-silico prediction, not a clinical call.

MORC2 p.Val413Phe

c.1237G>T · rs1602485677 · VCV804165

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.408 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.408	ambiguous
REVEL	0.457	indeterminate
SaProt	LLR -12.38	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 270 bp · p 7e-12 · regional, not allelic
Overall
CADD	23.8	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.Val413Phe
Coding: c.1237G>T
MANE Select: NM_001303256
dbSNP: rs1602485677
Type: single nucleotide variant
Location: chr22:30937947 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 9 PDB
Residue 413: a β-strand; a UniProt-annotated variant site (in digfan; increases hush-dependent gene silencing)

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

Similar variants

MORC2 p.Val413Ala Likely pathogenic 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-val413phe (accessed [today's date]).

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