Is NPM1 p.Ter295= (c.885A>G) pathogenic?

NPM1 p.Ter295= (c.885A>G) is classified Pathogenic in NPM1 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.00209%, nfe); Associated with acute myeloid leukemia.

What condition is associated with NPM1 p.Ter295= (c.885A>G)?

NPM1 p.Ter295= (c.885A>G) is associated with acute myeloid leukemia (ClinVar).

How common is NPM1 p.Ter295= (c.885A>G) in the general population?

NPM1 p.Ter295= (c.885A>G) is very rare (popmax 0.00209%, nfe) (gnomAD).

NPM1 p.Ter295=

c.885A>G · rs2113301391 · VCV1701937

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00209%, nfe)

Conditions

acute myeloid leukemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a LoF-intolerant gene
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Overall
CADD	11.83	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00209% European (non-Finnish) · 24/1,150,656 alleles

Filtering AF 0.00141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00119%

Overall 0.00171% 24/1,400,210 alleles · very rare

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: NPM1
Protein: p.Ter295=
Coding: c.885A>G
MANE Select: NM_002520
dbSNP: rs2113301391
Type: single nucleotide variant
Location: chr5:171410565 (GRCh38)
Gene constraint: LOEUF 0.313 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.42 · 8 PDB

Full NPM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

acute myeloid leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NPM1 c.847-5T>C Benign/Likely benign ★★ same condition
NPM1 p.Phe181= Benign/Likely benign ★★ same condition
NPM1 c.*101T>C Uncertain significance same condition
NPM1 c.*29A>T Uncertain significance same condition
NPM1 c.*2A>G Uncertain significance same condition
NPM1 c.*33T>C Uncertain significance same condition
NPM1 c.*73T>C Uncertain significance same condition
NPM1 c.*75C>T 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/npm1-p-ter295 (accessed [today's date]).

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