Is SAMD9 p.Lys894Glu (c.2680A>G) pathogenic?

SAMD9 p.Lys894Glu (c.2680A>G) is classified Benign in SAMD9 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0804); Common (popmax 7.39%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about SAMD9 p.Lys894Glu (c.2680A>G)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

SAMD9 p.Lys894Glu

Q: How common is SAMD9 p.Lys894Glu (c.2680A>G) in the general population?

SAMD9 p.Lys894Glu (c.2680A>G) is common (popmax 7.39%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2680A>G · rs79303965 · VCV791161

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.39%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -8.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7
Regional constraint	o/e 0.84	unconstrained · MANE · 2,122 bp · p 6.9e-06 · regional, not allelic
Overall
CADD	0.721	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

Grpmax group 7.39% African / African-American · 5,540/75,016 alleles

Filtering AF 7.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.16%

Overall 0.39% 6,288/1,613,388 alleles · common exomes 3,045/1,461,164 · genomes 3,243/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.39%	14
Admixed American	0.522%	191
Remaining individualsnot grpmax-eligible	0.48%	208
Middle Eastern	0.165%	606
South Asian	0.011%	9,106
European (non-Finnish)	0.00975%	10,256

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.Lys894Glu
Coding: c.2680A>G
MANE Select: NM_017654
dbSNP: rs79303965
Type: single nucleotide variant
Location: chr7:93103418 (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.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
SAMD9 p.Leu1511Ser Likely pathogenic ★★ ⚠ same type
SAMD9 p.Ala1057Val Uncertain significance ★★ ⚠ 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-lys894glu (accessed [today's date]).

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