Is POT1 p.Arg240= (c.720A>G) pathogenic?

POT1 p.Arg240= (c.720A>G) is classified Likely benign in POT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Very rare (popmax 0.00174%, amr); Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Arg240= (c.720A>G)?

POT1 p.Arg240= (c.720A>G) is associated with tumor predisposition syndrome 3, hereditary neoplastic syndrome (ClinVar).

How common is POT1 p.Arg240= (c.720A>G) in the general population?

POT1 p.Arg240= (c.720A>G) is very rare (popmax 0.00174%, amr) (gnomAD).

POT1 p.Arg240=

c.720A>G · rs766211616 · VCV826907

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00174%, amr)

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 0.61	GERP -3.9, phastCons 1
Overall
CADD	7.257	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00174% Admixed American · 1/57,478 alleles

Filtering AF 0.000889% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000727%

Overall 0.0012% 19/1,589,378 alleles · very rare exomes 18/1,437,256 · genomes 1/152,122 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00174%	57,478
European (non-Finnish)	0.00146%	68,494
African / African-American	0.00135%	73,928

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.Arg240=
Coding: c.720A>G
MANE Select: NM_015450
dbSNP: rs766211616
Type: single nucleotide variant
Location: chr7:124853121 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB
Residue 240: 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.Arg240Lys Uncertain significance ★ ⚠ same residue
POT1 p.Arg240fs Pathogenic ★ 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-arg240 (accessed [today's date]).

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