Is POT1 p.Ser2Phe (c.5C>T) pathogenic?

POT1 p.Ser2Phe (c.5C>T) is classified Uncertain significance in POT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-08). AlphaMissense: likely benign (0.2047); No allele count reported in gnomAD v4.1 (AN 1,453,220); Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Ser2Phe (c.5C>T)?

POT1 p.Ser2Phe (c.5C>T) is associated with tumor predisposition syndrome 3 (ClinVar).

How common is POT1 p.Ser2Phe (c.5C>T) in the general population?

POT1 p.Ser2Phe (c.5C>T) is no allele count reported in gnomAD v4.1 (AN 1,453,220) (gnomAD).

What do computational predictors say about POT1 p.Ser2Phe (c.5C>T)?

AlphaMissense predicts likely benign (score 0.2047) — an in-silico prediction, not a clinical call.

POT1 p.Ser2Phe

c.5C>T · rs2485575150 · VCV2863352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2047 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,453,220)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

tumor predisposition syndrome 3

Computational evidence

Protein change
AlphaMissense	0.2047	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 3.1, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 44 kb · p 1.3e-06 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,453,220). 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.Ser2Phe
Coding: c.5C>T
MANE Select: NM_015450
dbSNP: rs2485575150
Type: single nucleotide variant
Location: chr7:124897169 (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.Ser2Thr 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
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
POT1 c.1369+1G>A 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-ser2phe (accessed [today's date]).

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