Is POT1 p.Val4Asp (c.11T>A) pathogenic?

POT1 p.Val4Asp (c.11T>A) is classified Uncertain significance in POT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-08). AlphaMissense: likely benign (0.1576); Very rare (popmax 7.12e-05%); Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Val4Asp (c.11T>A)?

POT1 p.Val4Asp (c.11T>A) is associated with tumor predisposition syndrome 3 (ClinVar).

How common is POT1 p.Val4Asp (c.11T>A) in the general population?

POT1 p.Val4Asp (c.11T>A) is very rare (popmax 7.12e-05%) (gnomAD).

What do computational predictors say about POT1 p.Val4Asp (c.11T>A)?

AlphaMissense predicts likely benign (score 0.1576) — an in-silico prediction, not a clinical call.

POT1 p.Val4Asp

c.11T>A · rs2116630010 · VCV1518747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1576 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.12e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

tumor predisposition syndrome 3

Computational evidence

Protein change
AlphaMissense	0.1576	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -7.98	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 0.67	GERP 0.48, phastCons 0.95
Regional constraint	o/e 0.74	unconstrained · MANE · 44 kb · p 1.3e-06 · regional, not allelic
Overall
CADD	20.7	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

Grpmax group 7.12e-05%

Overall 7.12e-05% 1/1,404,092 alleles · very rare exomes 1/1,252,390 · genomes 0/151,702 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: POT1
Protein: p.Val4Asp
Coding: c.11T>A
MANE Select: NM_015450
dbSNP: rs2116630010
Type: single nucleotide variant
Location: chr7:124892379 (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.Val4fs Pathogenic ★ same residue
POT1 p.Val4Ile 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-val4asp (accessed [today's date]).

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