Is POT1 p.Arg137= (c.411T>G) pathogenic?

POT1 p.Arg137= (c.411T>G) is classified Likely benign in POT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-23). Absent from gnomAD v4.1; Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Arg137= (c.411T>G)?

POT1 p.Arg137= (c.411T>G) is associated with tumor predisposition syndrome 3 (ClinVar).

How common is POT1 p.Arg137= (c.411T>G) in the general population?

POT1 p.Arg137= (c.411T>G) is absent from gnomAD v4.1 (gnomAD).

POT1 p.Arg137=

c.411T>G · rs2116541924 · VCV1095747

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

tumor predisposition syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -3.6, phastCons 0.006
Overall
CADD	7.902	PHRED · no single calibrated threshold — expert panels disagree

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: POT1
Protein: p.Arg137=
Coding: c.411T>G
MANE Select: NM_015450
dbSNP: rs2116541924
Type: single nucleotide variant
Location: chr7:124863485 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB
Residue 137: a UniProt-annotated variant site (in tpds3; increased telomere intensity signals and telomere fragility); 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.Arg137Cys Uncertain significance ★★ ⚠ same residue
POT1 p.Arg137His Uncertain significance ★★ ⚠ same residue
POT1 p.Arg137Leu 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-arg137 (accessed [today's date]).

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