Is MORC2 p.Ala313= (c.939T>A) pathogenic?

MORC2 p.Ala313= (c.939T>A) is classified Benign/Likely benign in MORC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-01). Rare (popmax 0.165%, sas); Associated with Charcot-Marie-Tooth disease axonal type 2Z.

What condition is associated with MORC2 p.Ala313= (c.939T>A)?

MORC2 p.Ala313= (c.939T>A) is associated with Charcot-Marie-Tooth disease axonal type 2Z (ClinVar).

How common is MORC2 p.Ala313= (c.939T>A) in the general population?

MORC2 p.Ala313= (c.939T>A) is rare (popmax 0.165%, sas) (gnomAD).

MORC2 p.Ala313=

Q: How is Autosomal dominant Charcot-Marie-Tooth disease type 2Z inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.939T>A · rs755275051 · VCV1636426

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.165%, sas)

Conditions

Charcot-Marie-Tooth disease axonal type 2Z

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	GERP -0.61, phastCons 0.99
Overall
CADD	10.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.165% South Asian · 150/91,084 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.0107% 172/1,613,864 alleles · rare exomes 168/1,461,664 · genomes 4/152,200 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.165%	607
Middle Eastern	0.0657%	1,521
Remaining individualsnot grpmax-eligible	0.008%	12,496
Admixed American	0.00167%	60,014
European (non-Finnish)	0.00102%	98,336

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.Ala313=
Coding: c.939T>A
MANE Select: NM_001303256
dbSNP: rs755275051
Type: single nucleotide variant
Location: chr22:30940007 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 9 PDB
Residue 313: an α-helix

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

Disease context

Charcot-Marie-Tooth disease axonal type 2Z — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant Charcot-Marie-Tooth disease type 2Z (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal

Similar variants

MORC2 p.Arg132Cys 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
MORC2 p.Thr24Ile 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-ala313 (accessed [today's date]).

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