Is MORC2 p.Ala152Pro (c.454G>C) pathogenic?

MORC2 p.Ala152Pro (c.454G>C) is classified Uncertain significance in MORC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-22). AlphaMissense: likely benign (0.2613); Very rare (popmax 0.00144%, nfe).

How common is MORC2 p.Ala152Pro (c.454G>C) in the general population?

MORC2 p.Ala152Pro (c.454G>C) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about MORC2 p.Ala152Pro (c.454G>C)?

AlphaMissense predicts likely benign (score 0.2613) — an in-silico prediction, not a clinical call.

MORC2 p.Ala152Pro

c.454G>C · VCV4947424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2613	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -12.13	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP -1.8, phastCons 0.98
Regional constraint	o/e 0.74	unconstrained · MANE · 8,285 bp · p 7.2e-07 · regional, not allelic
Overall
CADD	20.5	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 0.00144% European (non-Finnish) · 17/1,179,976 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00112% 18/1,612,944 alleles · very rare exomes 18/1,460,604 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00144%	69,410
African / African-American	0.00133%	75,042

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.Ala152Pro
Coding: c.454G>C
MANE Select: NM_001303256
Type: single nucleotide variant
Location: chr22:30942244 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 9 PDB
Residue 152: a turn

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-ala152pro (accessed [today's date]).

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