Is SAMD9 p.Lys620= (c.1860A>G) pathogenic?

SAMD9 p.Lys620= (c.1860A>G) is classified Benign/Likely benign in SAMD9 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.42%, eas); Associated with monosomy 7 myelodysplasia and leukemia syndrome 2.

What condition is associated with SAMD9 p.Lys620= (c.1860A>G)?

SAMD9 p.Lys620= (c.1860A>G) is associated with monosomy 7 myelodysplasia and leukemia syndrome 2, normophosphatemic familial tumoral calcinosis, MIRAGE syndrome (ClinVar).

How common is SAMD9 p.Lys620= (c.1860A>G) in the general population?

SAMD9 p.Lys620= (c.1860A>G) is low-frequency (popmax 2.42%, eas) (gnomAD).

SAMD9 p.Lys620=

c.1860A>G · rs77922936 · VCV731185

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.42%, eas)

Conditions

monosomy 7 myelodysplasia and leukemia syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.55	phastCons 0.99
Overall
CADD	4.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.42% East Asian · 1,086/44,868 alleles

Filtering AF 2.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.25%

Overall 0.0751% 1,212/1,613,854 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.42%	41
Remaining individualsnot grpmax-eligible	0.104%	961
South Asian	0.0505%	1,980
Middle Eastern	0.033%	3,031
Admixed American	0.005%	20,003
European (non-Finnish)	0.000848%	117,983

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: SAMD9
Protein: p.Lys620=
Coding: c.1860A>G
MANE Select: NM_017654
dbSNP: rs77922936
Type: single nucleotide variant
Location: chr7:93104238 (GRCh38)
Gene constraint: LOEUF 1.773 · pLI 0.03 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 83.79 · 10 PDB

Full SAMD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

monosomy 7 myelodysplasia and leukemia syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: normophosphatemic familial tumoral calcinosis MIRAGE syndrome

For Familial monosomy 7 syndrome (Orphanet):

Onset: Childhood, Infancy

Similar variants

SAMD9 p.Lys620Arg Uncertain significance ★★ ⚠ same residue
SAMD9 p.Lys620Gln Uncertain significance ★ ⚠ same residue
SAMD9 p.Lys620Ile Uncertain significance ★ ⚠ same residue
SAMD9 p.Arg1293Trp Pathogenic ★★ ⚠ same condition
SAMD9 p.Arg459Gln Pathogenic ★★ ⚠ same condition
SAMD9 p.Arg685Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
SAMD9 p.Arg824Gln Pathogenic ★★ ⚠ same condition
SAMD9 p.Arg982Cys Pathogenic/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/samd9-p-lys620 (accessed [today's date]).

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