Is MLC1 p.Pro241= (c.723A>G) pathogenic?

MLC1 p.Pro241= (c.723A>G) is classified Uncertain significance in MLC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-13). No allele count reported in gnomAD v4.1 (AN 1,563,474); Associated with megalencephalic leukoencephalopathy with subcortical cysts.

What condition is associated with MLC1 p.Pro241= (c.723A>G)?

MLC1 p.Pro241= (c.723A>G) is associated with megalencephalic leukoencephalopathy with subcortical cysts (ClinVar).

How common is MLC1 p.Pro241= (c.723A>G) in the general population?

MLC1 p.Pro241= (c.723A>G) is no allele count reported in gnomAD v4.1 (AN 1,563,474) (gnomAD).

MLC1 p.Pro241=

Q: How is Megalencephalic leukoencephalopathy with subcortical cysts inherited?

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

c.723A>G · VCV4057764

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,563,474)

Conditions

megalencephalic leukoencephalopathy with subcortical cysts

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 -5.2	GERP -2.5
Overall
CADD	5.931	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,563,474). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MLC1
Protein: p.Pro241=
Coding: c.723A>G
MANE Select: NM_015166
Type: single nucleotide variant
Location: chr22:50070575 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.29

Full MLC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

megalencephalic leukoencephalopathy with subcortical cysts — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Megalencephalic leukoencephalopathy with subcortical cysts (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

MLC1 c.1059+1G>A Likely pathogenic ★★ same condition
MLC1 c.321+1G>A Likely pathogenic ★★ same condition
MLC1 c.321+2T>G Likely pathogenic ★★ same condition
MLC1 c.423+1G>A Pathogenic/Likely pathogenic ★★ same condition
MLC1 c.423+1G>T Pathogenic/Likely pathogenic ★★ same condition
MLC1 c.597+1G>A Pathogenic/Likely pathogenic ★★ same condition
MLC1 c.597+2T>C Likely pathogenic ★★ same condition
MLC1 c.714+1G>A 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/mlc1-p-pro241 (accessed [today's date]).

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