Is MLC1 p.Val75fs (c.223del) pathogenic?

MLC1 p.Val75fs (c.223del) is classified Pathogenic in MLC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-01-03). No gnomAD frequency available for this variant; Associated with megalencephalic leukoencephalopathy with subcortical cysts 1.

What condition is associated with MLC1 p.Val75fs (c.223del)?

MLC1 p.Val75fs (c.223del) is associated with megalencephalic leukoencephalopathy with subcortical cysts 1 (ClinVar).

How common is MLC1 p.Val75fs (c.223del) in the general population?

MLC1 p.Val75fs (c.223del) is no gnomAD frequency available for this variant (gnomAD).

MLC1 p.Val75fs

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.223del · rs794729233 · VCV202208

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

megalencephalic leukoencephalopathy with subcortical cysts 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Val75fs
Coding: c.223del
MANE Select: NM_015166
dbSNP: rs794729233
Type: Deletion
Location: chr22:50083128 (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 1 — 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.177+1del Pathogenic/Likely pathogenic ★★ same condition
MLC1 p.Ile283_Met284insTer Pathogenic/Likely pathogenic ★★ same condition
MLC1 p.Leu150fs Pathogenic ★★ same condition
MLC1 p.Ser197_Tyr198insTer Pathogenic ★★ same condition
MLC1 p.Ser246fs Pathogenic ★★ same condition
MLC1 p.Ser254fs Likely pathogenic ★★ same condition
MLC1 p.Asn110fs Pathogenic ★ same condition
MLC1 p.Asp31fs 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-val75fs (accessed [today's date]).

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