SACM1L

Chr 3

SAC1 like phosphatidylinositide phosphatase

Also known as: SAC1

The protein functions as a phosphoinositide phosphatase that hydrolyzes phosphatidylinositol 4-phosphate and other phosphoinositides, playing a critical role in cellular membrane organization. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and brain malformations. The gene shows high constraint against loss-of-function variants (LOEUF 0.37), consistent with its essential role in early development.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.37
Clinical SummarySACM1L
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.70) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 57 VUS of 83 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.37LOEUF
pLI 0.695
Z-score 4.60
OE 0.20 (0.120.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.99Z-score
OE missense 0.68 (0.610.76)
209 obs / 307.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.120.37)
00.351.4
Missense OE0.68 (0.610.76)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 8 / 39.0Missense obs/exp: 209 / 307.2Syn Z: 0.75

ClinVar Variant Classifications

83 submitted variants in ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS57
Likely Benign3
6
Pathogenic
1
Likely Pathogenic
57
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
1
0
1
VUS
1
55
1
0
57
Likely Benign
0
2
1
0
3
Benign
0
0
0
0
0
Total1579067

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SACM1L · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC