Is MORC2 p.Ala78= (c.234T>G) pathogenic?

MORC2 p.Ala78= (c.234T>G) is classified Benign/Likely benign in MORC2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.87%, amr); Associated with developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy.

How common is MORC2 p.Ala78= (c.234T>G) in the general population?

MORC2 p.Ala78= (c.234T>G) is low-frequency (popmax 3.87%, amr) (gnomAD).

MORC2 p.Ala78=

Q: What condition is associated with MORC2 p.Ala78= (c.234T>G)?

MORC2 p.Ala78= (c.234T>G) is associated with developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy, Charcot-Marie-Tooth disease axonal type 2Z (ClinVar).

c.234T>G · rs140792905 · VCV475598

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.87%, amr)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -0.53, phastCons 1
Overall
CADD	8.886	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.87% Admixed American · 2,322/60,016 alleles

Filtering AF 3.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.68%

Overall 0.417% 6,733/1,614,092 alleles · low-frequency exomes 5,858/1,461,772 · genomes 875/152,320 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	3.87%	26
Finnishnot grpmax-eligible	3.34%	30
Ashkenazi Jewishnot grpmax-eligible	0.473%	211
Remaining individualsnot grpmax-eligible	0.338%	296
European (non-Finnish)	0.155%	647
South Asian	0.0582%	1,719
African / African-American	0.0546%	1,830
Middle Eastern	0.033%	3,031

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.Ala78=
Coding: c.234T>G
MANE Select: NM_001303256
dbSNP: rs140792905
Type: single nucleotide variant
Location: chr22:30949835 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 9 PDB
Residue 78: 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.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
MORC2 p.Ser87Leu 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-ala78 (accessed [today's date]).

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