Is SAMD9 p.Ile448= (c.1344C>A) pathogenic?

SAMD9 p.Ile448= (c.1344C>A) is classified Likely benign in SAMD9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-22). Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with SAMD9 p.Ile448= (c.1344C>A)?

SAMD9 p.Ile448= (c.1344C>A) is associated with Inborn genetic diseases (ClinVar).

How common is SAMD9 p.Ile448= (c.1344C>A) in the general population?

SAMD9 p.Ile448= (c.1344C>A) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

SAMD9 p.Ile448=

c.1344C>A · rs756486791 · VCV1648671

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, 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 0.34
Overall
CADD	0.429	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,870 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000434% 7/1,613,674 alleles · ultra-rare exomes 6/1,461,604 · genomes 1/152,070 · joint denominator

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.Ile448=
Coding: c.1344C>A
MANE Select: NM_017654
dbSNP: rs756486791
Type: single nucleotide variant
Location: chr7:93104754 (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.Ile448Val Uncertain significance ★★ ⚠ same residue
SAMD9 p.Ile448Phe Uncertain significance ★ ⚠ same residue
SAMD9 p.Ile448Met 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

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-ile448 (accessed [today's date]).

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