Is POT1 p.Phe31Ser (c.92T>C) pathogenic?

POT1 p.Phe31Ser (c.92T>C) is classified Uncertain significance in POT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-19). AlphaMissense: likely pathogenic (0.9587); No allele count reported in gnomAD v4.1 (AN 1,548,354); Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Phe31Ser (c.92T>C)?

POT1 p.Phe31Ser (c.92T>C) is associated with tumor predisposition syndrome 3 (ClinVar).

How common is POT1 p.Phe31Ser (c.92T>C) in the general population?

POT1 p.Phe31Ser (c.92T>C) is no allele count reported in gnomAD v4.1 (AN 1,548,354) (gnomAD).

What do computational predictors say about POT1 p.Phe31Ser (c.92T>C)?

AlphaMissense predicts likely pathogenic (score 0.9587) — an in-silico prediction, not a clinical call.

POT1 p.Phe31Ser

c.92T>C · rs1489113369 · VCV1476063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9587 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,548,354)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

tumor predisposition syndrome 3

Computational evidence

Protein change
AlphaMissense	0.9587	likely pathogenic · top 5% in POT1
REVEL	0.456	indeterminate
SaProt	LLR -1.57	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 44 kb · p 1.3e-06 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

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 1,548,354). 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.Phe31Ser
Coding: c.92T>C
MANE Select: NM_015450
dbSNP: rs1489113369
Type: single nucleotide variant
Location: chr7:124892298 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB
Residue 31: 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

Similar variants

POT1 p.Phe31Cys Uncertain significance ★★ ⚠ same residue
POT1 p.Phe31Leu Uncertain significance ★ ⚠ same residue
POT1 p.Phe31= Likely benign ★ 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-phe31ser (accessed [today's date]).

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