Is POT1 p.Pro383= (c.1149T>C) pathogenic?

POT1 p.Pro383= (c.1149T>C) is classified Likely benign in POT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). Absent from gnomAD v4.1; Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Pro383= (c.1149T>C)?

POT1 p.Pro383= (c.1149T>C) is associated with tumor predisposition syndrome 3 (ClinVar).

How common is POT1 p.Pro383= (c.1149T>C) in the general population?

POT1 p.Pro383= (c.1149T>C) is absent from gnomAD v4.1 (gnomAD).

POT1 p.Pro383=

c.1149T>C · rs2485401639 · VCV2832346

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 0.69	GERP -0.89, phastCons 0.94
Overall
CADD	8.414	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.Pro383=
Coding: c.1149T>C
MANE Select: NM_015450
dbSNP: rs2485401639
Type: single nucleotide variant
Location: chr7:124842821 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB
Residue 383: a turn

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.Pro383Thr Uncertain significance ★★ ⚠ same residue
POT1 p.Pro383Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
POT1 p.Pro383fs 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

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-pro383 (accessed [today's date]).

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