Is POT1 p.Val50= (c.150G>A) pathogenic?

POT1 p.Val50= (c.150G>A) is classified Uncertain significance in POT1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-20). Very rare (popmax 8.5e-05%, nfe); Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Val50= (c.150G>A)?

POT1 p.Val50= (c.150G>A) is associated with tumor predisposition syndrome 3, hereditary neoplastic syndrome (ClinVar).

How common is POT1 p.Val50= (c.150G>A) in the general population?

POT1 p.Val50= (c.150G>A) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

POT1 p.Val50=

c.150G>A · rs1795855228 · VCV1308859

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Conditions

tumor predisposition syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.44	acceptor loss · deltas
Pangolin	Δ0.49	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.1	GERP 1.1, phastCons 1
Overall
CADD	2.293	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,176 alleles

Overall 6.22e-05% 1/1,607,610 alleles · very rare exomes 1/1,455,486 · genomes 0/152,124 · 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: POT1
Protein: p.Val50=
Coding: c.150G>A
MANE Select: NM_015450
dbSNP: rs1795855228
Type: single nucleotide variant
Location: chr7:124871016 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB
Residue 50: a β-strand

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

Also linked: hereditary neoplastic syndrome

Similar variants

POT1 p.Val50Leu Uncertain significance ★★ ⚠ same residue
POT1 p.Val50Met 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
POT1 c.125-2A>G 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-val50 (accessed [today's date]).

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