Is POT1 p.Arg80= (c.240C>T) pathogenic?

POT1 p.Arg80= (c.240C>T) is classified Likely benign in POT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-24). Very rare (popmax 0.00134%, afr); Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Arg80= (c.240C>T)?

POT1 p.Arg80= (c.240C>T) is associated with tumor predisposition syndrome 3 (ClinVar).

How common is POT1 p.Arg80= (c.240C>T) in the general population?

POT1 p.Arg80= (c.240C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

POT1 p.Arg80=

c.240C>T · rs1554429181 · VCV475075

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

tumor predisposition syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -3, phastCons 1
Overall
CADD	7.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,734 alleles

Overall 6.22e-05% 1/1,606,594 alleles · very rare exomes 1/1,454,410 · genomes 0/152,184 · 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.Arg80=
Coding: c.240C>T
MANE Select: NM_015450
dbSNP: rs1554429181
Type: single nucleotide variant
Location: chr7:124870926 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB
Residue 80: 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

Similar variants

POT1 p.Arg80His Uncertain significance ★★ ⚠ same residue
POT1 p.Arg80Cys Conflicting classifications of pathogenicity ★ same residue
POT1 p.Arg80Gly Uncertain significance ★ ⚠ same residue
POT1 p.Arg80Leu Uncertain significance ★ ⚠ same residue
POT1 p.Arg80Ser 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

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-arg80 (accessed [today's date]).

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