Is SAMD9 p.Lys72= (c.216A>G) pathogenic?

SAMD9 p.Lys72= (c.216A>G) is classified Likely benign in SAMD9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-21). Ultra-rare (popmax 0.0735%, eas); Associated with Inborn genetic diseases.

What condition is associated with SAMD9 p.Lys72= (c.216A>G)?

SAMD9 p.Lys72= (c.216A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SAMD9 p.Lys72= (c.216A>G) in the general population?

SAMD9 p.Lys72= (c.216A>G) is ultra-rare (popmax 0.0735%, eas) (gnomAD).

SAMD9 p.Lys72=

c.216A>G · rs199597506 · VCV1967202

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0735%, eas)

Conditions

Inborn genetic diseases

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 -1.3	GERP -4.4
Overall
CADD	1.548	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0735% East Asian · 33/44,868 alleles

Filtering AF 0.0538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0471%

Overall 0.0039% 63/1,614,162 alleles · ultra-rare exomes 54/1,461,792 · genomes 9/152,370 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0735%	1,360
South Asian	0.0285%	3,503
Remaining individualsnot grpmax-eligible	0.0064%	15,627

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.Lys72=
Coding: c.216A>G
MANE Select: NM_017654
dbSNP: rs199597506
Type: single nucleotide variant
Location: chr7:93105882 (GRCh38)
Gene constraint: LOEUF 1.773 · pLI 0.03 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 83.79 · 10 PDB
Residue 72: the sam domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SAMD9 p.Ala1057Val Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala1066Thr Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala1069Thr Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala1082Gly Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala1102Asp Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala1195Asp Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala123Ser Uncertain significance ★★ ⚠ same condition
SAMD9 p.Ala1290Val Uncertain significance ★★ ⚠ 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-lys72 (accessed [today's date]).

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