SAMD1

Chr 19

sterile alpha motif domain containing 1

The protein binds to unmethylated CpG islands and acts as a transcriptional repressor by recruiting histone-modifying complexes to regulate chromatin structure. Biallelic mutations in SAMD1 cause a severe neurodevelopmental disorder with early infantile onset characterized by intellectual disability, seizures, and brain malformations. This gene follows autosomal recessive inheritance and shows moderate constraint against loss-of-function variants.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
12
P/LP submissions
0%
P/LP missense
0.67
LOEUF
Mechanism
Clinical SummarySAMD1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 18 VUS of 38 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.67LOEUF
pLI 0.236
Z-score 2.35
OE 0.26 (0.120.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.06Z-score
OE missense 0.99 (0.871.13)
159 obs / 161.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.120.67)
00.351.4
Missense OE0.99 (0.871.13)
00.61.4
Synonymous OE1.48
01.21.6
LoF obs/exp: 3 / 11.7Missense obs/exp: 159 / 161.1Syn Z: -3.16

ClinVar Variant Classifications

38 submitted variants in ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS18
Likely Benign4
11
Pathogenic
1
Likely Pathogenic
18
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
1
0
1
VUS
0
15
3
0
18
Likely Benign
0
0
1
3
4
Benign
0
0
0
0
0
Total01516334

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

View in ClinVar →

Protein Context — Lollipop Plot

SAMD1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗