Is POT1 p.Glu450Ter (c.1348G>T) pathogenic?

POT1 p.Glu450Ter (c.1348G>T) is classified Pathogenic in POT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-12-07). No allele count reported in gnomAD v4.1 (AN 1,607,316); Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Glu450Ter (c.1348G>T)?

POT1 p.Glu450Ter (c.1348G>T) is associated with tumor predisposition syndrome 3 (ClinVar).

How common is POT1 p.Glu450Ter (c.1348G>T) in the general population?

POT1 p.Glu450Ter (c.1348G>T) is no allele count reported in gnomAD v4.1 (AN 1,607,316) (gnomAD).

POT1 p.Glu450Ter

c.1348G>T · rs797045169 · VCV209094

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,316)

Conditions

tumor predisposition syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.28	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4	GERP 0.81, phastCons 1
Overall
CADD	37.0	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

No allele count reported in gnomAD v4.1 (AN 1,607,316). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: POT1
Protein: p.Glu450Ter
Coding: c.1348G>T
MANE Select: NM_015450
dbSNP: rs797045169
Type: single nucleotide variant
Location: chr7:124840994 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB
Residue 450: an α-helix

Full POT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tumor predisposition syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

POT1 p.Glu450= Likely benign ★★ same residue
POT1 p.Glu450Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
POT1 p.Glu450Gly Uncertain significance ★ ⚠ same residue
POT1 c.10-2A>C Pathogenic/Likely pathogenic ★★ same condition
POT1 c.1163+1G>A Likely pathogenic ★★ same condition
POT1 c.1164-1G>A Pathogenic/Likely pathogenic ★★ same condition
POT1 c.124+1G>C Pathogenic/Likely pathogenic ★★ same condition
POT1 c.124+2T>C Likely pathogenic ★★ 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/pot1-p-glu450ter (accessed [today's date]).

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