Is MLC1 p.Ser93= (c.279G>T) pathogenic?

MLC1 p.Ser93= (c.279G>T) is classified Likely benign in MLC1 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-12-30). Very rare (popmax 0.00112%, sas); Associated with megalencephalic leukoencephalopathy with subcortical cysts.

What condition is associated with MLC1 p.Ser93= (c.279G>T)?

MLC1 p.Ser93= (c.279G>T) is associated with megalencephalic leukoencephalopathy with subcortical cysts (ClinVar).

How common is MLC1 p.Ser93= (c.279G>T) in the general population?

MLC1 p.Ser93= (c.279G>T) is very rare (popmax 0.00112%, sas) (gnomAD).

MLC1 p.Ser93=

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.279G>T · rs11568172 · VCV1530562

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

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 -9.6	GERP -2.8
Overall
CADD	0.057	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,212 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000311% 5/1,605,266 alleles · very rare exomes 5/1,452,912 · genomes 0/152,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00112%	89,212
European (non-Finnish)	0.00034%	293,983

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: MLC1
Protein: p.Ser93=
Coding: c.279G>T
MANE Select: NM_015166
dbSNP: rs11568172
Type: single nucleotide variant
Location: chr22:50080386 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.29
Residue 93: a UniProt-annotated variant site (in mlc1)

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 p.Ser93Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
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

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-ser93 (accessed [today's date]).

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