Is POT1 p.Val28Ile (c.82G>A) pathogenic?

POT1 p.Val28Ile (c.82G>A) is classified Likely benign in POT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-22). AlphaMissense: likely benign (0.083); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with POT1 p.Val28Ile (c.82G>A)?

POT1 p.Val28Ile (c.82G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is POT1 p.Val28Ile (c.82G>A) in the general population?

POT1 p.Val28Ile (c.82G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about POT1 p.Val28Ile (c.82G>A)?

AlphaMissense predicts likely benign (score 0.083) — an in-silico prediction, not a clinical call.

POT1 p.Val28Ile

c.82G>A · VCV4862393

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.083 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.083	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -7.64	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 1.4	GERP 0.97, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 44 kb · p 1.3e-06 · regional, not allelic
Overall
CADD	18.1	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

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.Val28Ile
Coding: c.82G>A
MANE Select: NM_015450
Type: single nucleotide variant
Location: chr7:124892308 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB
Residue 28: a β-strand

Full POT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

POT1 p.Val28fs 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
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-val28ile (accessed [today's date]).

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