Is SAMD9 p.Ile718= (c.2154T>C) pathogenic?

SAMD9 p.Ile718= (c.2154T>C) is classified Likely benign in SAMD9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-22). Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with SAMD9 p.Ile718= (c.2154T>C)?

SAMD9 p.Ile718= (c.2154T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SAMD9 p.Ile718= (c.2154T>C) in the general population?

SAMD9 p.Ile718= (c.2154T>C) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

SAMD9 p.Ile718=

c.2154T>C · rs769881400 · VCV1945070

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, 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 -0.17
Overall
CADD	2.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,868 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00093% 15/1,613,422 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,608
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0032%	31,236
South Asian	0.0011%	91,074
European (non-Finnish)	0.000254%	393,164

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.Ile718=
Coding: c.2154T>C
MANE Select: NM_017654
dbSNP: rs769881400
Type: single nucleotide variant
Location: chr7:93103944 (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

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

Similar variants

SAMD9 p.Ile718Thr Uncertain significance ★★ ⚠ same residue
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

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-ile718 (accessed [today's date]).

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