Is POT1 p.Val4fs (c.2_9dup) pathogenic?

POT1 p.Val4fs (c.29dup) is classified Pathogenic in POT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). No gnomAD frequency available for this variant; Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Val4fs (c.2_9dup)?

POT1 p.Val4fs (c.2_9dup) is associated with tumor predisposition syndrome 3 (ClinVar).

How common is POT1 p.Val4fs (c.2_9dup) in the general population?

POT1 p.Val4fs (c.2_9dup) is no gnomAD frequency available for this variant (gnomAD).

POT1 p.Val4fs

c.2_9dup · rs1796511665 · VCV939360

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

tumor predisposition syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 3.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: POT1
Protein: p.Val4fs
Coding: c.2_9dup
MANE Select: NM_015450
dbSNP: rs1796511665
Type: Duplication
Location: chr7:124897164 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB

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.Val4Gly Uncertain significance ★★ ⚠ same residue
POT1 p.Val4Asp Uncertain significance ★ ⚠ same residue
POT1 p.Asn441fs Pathogenic/Likely pathogenic ★★ same condition
POT1 p.Asn54fs Pathogenic/Likely pathogenic ★★ same condition
POT1 p.Asp304fs Pathogenic/Likely pathogenic ★★ same condition
POT1 p.Cys506fs Pathogenic ★★ same condition
POT1 p.Gln358fs Pathogenic/Likely pathogenic ★★ same condition
POT1 p.Gly319fs 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-val4fs (accessed [today's date]).

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