SAMD7

Chr 3AR

sterile alpha motif domain containing 7

Also known as: MDCD

NCBI Gene: 344658 ENSG00000187033 UniProt: Q7Z3H4 OMIM: 620493

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific; chromatin binding activity; and histone binding activity. Predicted to be involved in negative regulation of DNA-templated transcription; negative regulation of gene expression, epigenetic; and retinal rod cell development. Predicted to be located in cytoplasm. Predicted to be part of PRC1 complex. Predicted to be active in nucleus. Implicated in macular degeneration. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.051 OMIM phenotype

Clinical Summary— SAMD7

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 58 VUS of 69 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.39

OE 0.65 (0.42–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.18Z-score

OE missense 0.97 (0.87–1.08)

241 obs / 249.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.42–1.05)

0≤0.351.4

Missense OE?0.97 (0.87–1.08)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 12 / 18.4Missense obs/exp: 241 / 249.0Syn Z: -0.10

This gene — mechanism propensity

0.6551th %ile

GOF

0.5267th %ile

LOF

0.3842th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

VUS58

Likely Benign3

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	4	2	6
Likely Pathogenic	0	0	0
VUS	0	58	58
Likely Benign	0	3	3
Benign	0	0	0
Total	4	63	67

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap SAMD7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →