Is SAMD9 p.Phe882Val (c.2644T>G) pathogenic?

SAMD9 p.Phe882Val (c.2644T>G) is classified Likely pathogenic in SAMD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). AlphaMissense: likely pathogenic (0.6651); Absent from gnomAD v4.1.

How common is SAMD9 p.Phe882Val (c.2644T>G) in the general population?

SAMD9 p.Phe882Val (c.2644T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SAMD9 p.Phe882Val (c.2644T>G)?

AlphaMissense predicts likely pathogenic (score 0.6651) — an in-silico prediction, not a clinical call.

SAMD9 p.Phe882Val

c.2644T>G · rs2116417034 · VCV1695195

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6651 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6651	likely pathogenic ✓ concordant with ClinVar
REVEL	0.208	benign-leaning
SaProt	LLR -7.90	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.17	constrained · MANE · 53 bp · p 0.00042 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SAMD9
Protein: p.Phe882Val
Coding: c.2644T>G
MANE Select: NM_017654
dbSNP: rs2116417034
Type: single nucleotide variant
Location: chr7:93103454 (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

Similar variants

SAMD9 p.Phe882Cys Uncertain significance ★★ ⚠ same residue
SAMD9 p.Phe882Leu Uncertain significance ★ ⚠ same residue
SAMD9 p.Arg1293Trp Pathogenic ★★ ⚠ same type
SAMD9 p.Arg459Gln Pathogenic ★★ ⚠ same type
SAMD9 p.Arg685Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
SAMD9 p.Arg824Gln Pathogenic ★★ ⚠ same type
SAMD9 p.Arg982Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
SAMD9 p.Arg982His Pathogenic/Likely pathogenic ★★ ⚠ same type

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-phe882val (accessed [today's date]).

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