Is MORC2 p.Ala40Val (c.119C>T) pathogenic?

MORC2 p.Ala40Val (c.119C>T) is classified Uncertain significance in MORC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-05). AlphaMissense: likely pathogenic (0.9882); Absent from gnomAD v4.1.

How common is MORC2 p.Ala40Val (c.119C>T) in the general population?

MORC2 p.Ala40Val (c.119C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MORC2 p.Ala40Val (c.119C>T)?

AlphaMissense predicts likely pathogenic (score 0.9882) — an in-silico prediction, not a clinical call.

MORC2 p.Ala40Val

c.119C>T · rs2517643332 · VCV1710818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9882 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9882	likely pathogenic · top 10% in MORC2
REVEL	0.743	pathogenic-leaning
SaProt	LLR -13.21	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 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 8,864 bp · p 0.081 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Ala40Val
Coding: c.119C>T
MANE Select: NM_001303256
dbSNP: rs2517643332
Type: single nucleotide variant
Location: chr22:30958644 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 9 PDB
Residue 40: an α-helix

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-ala40val (accessed [today's date]).

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