Is POT1 p.Asp598= (c.1794T>C) pathogenic?

POT1 p.Asp598= (c.1794T>C) is classified Likely benign in POT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-08). Very rare (popmax 8.69e-05%, nfe); Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Asp598= (c.1794T>C)?

POT1 p.Asp598= (c.1794T>C) is associated with tumor predisposition syndrome 3 (ClinVar).

How common is POT1 p.Asp598= (c.1794T>C) in the general population?

POT1 p.Asp598= (c.1794T>C) is very rare (popmax 8.69e-05%, nfe) (gnomAD).

POT1 p.Asp598=

c.1794T>C · rs2116403728 · VCV1085633

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.69e-05%, nfe)

Conditions

tumor predisposition syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.148	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5	GERP 1.8, phastCons 1
Overall
CADD	13.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.69e-05% European (non-Finnish) · 1/1,150,960 alleles

Overall 6.35e-05% 1/1,573,854 alleles · very rare exomes 1/1,421,660 · genomes 0/152,194 · 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.Asp598=
Coding: c.1794T>C
MANE Select: NM_015450
dbSNP: rs2116403728
Type: single nucleotide variant
Location: chr7:124824073 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB
Residue 598: 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.Asp598Gly Uncertain significance ★★ ⚠ same residue
POT1 p.Asp598Asn Uncertain significance ★ ⚠ same residue
POT1 p.Asp598His Uncertain significance ★ ⚠ same residue
POT1 p.Asp598Val Uncertain significance ★ ⚠ same residue
POT1 p.Asp598fs 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-asp598 (accessed [today's date]).

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