Is MORC2 p.Val298= (c.894A>G) pathogenic?

MORC2 p.Val298= (c.894A>G) is classified Benign/Likely benign in MORC2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-14). Rare (popmax 0.676%, sas); Associated with developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy.

How common is MORC2 p.Val298= (c.894A>G) in the general population?

MORC2 p.Val298= (c.894A>G) is rare (popmax 0.676%, sas) (gnomAD).

MORC2 p.Val298=

Q: What condition is associated with MORC2 p.Val298= (c.894A>G)?

MORC2 p.Val298= (c.894A>G) is associated with developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy, Charcot-Marie-Tooth disease axonal type 2Z (ClinVar).

c.894A>G · rs562612569 · VCV772359

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.676%, sas)

Conditions

developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.35	GERP -3.7, phastCons 0.23
Overall
CADD	7.024	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.676% South Asian · 616/91,086 alleles

Filtering AF 0.632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.614%

Overall 0.0422% 681/1,614,132 alleles · rare exomes 643/1,461,856 · genomes 38/152,276 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.676%	148
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Finnishnot grpmax-eligible	0.00468%	21,345
European (non-Finnish)	0.00297%	33,714

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.Val298=
Coding: c.894A>G
MANE Select: NM_001303256
dbSNP: rs562612569
Type: single nucleotide variant
Location: chr22:30940768 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 9 PDB
Residue 298: an α-helix

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

Disease context

developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease axonal type 2Z

Similar variants

MORC2 p.Val298Leu Uncertain significance ★★ ⚠ same residue
MORC2 p.Arg132Cys Pathogenic/Likely pathogenic ★★ same condition
MORC2 p.Arg132His Pathogenic/Likely pathogenic ★★ ⚠ same condition
MORC2 p.Arg252Trp Pathogenic/Likely pathogenic ★★ same condition
MORC2 p.Arg266Ser Pathogenic/Likely pathogenic ★★ same condition
MORC2 p.Asp466Asn Pathogenic/Likely pathogenic ★★ ⚠ same condition
MORC2 p.Glu236Gly Pathogenic/Likely pathogenic ★★ same condition
MORC2 p.Glu27Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition

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-val298 (accessed [today's date]).

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