Is POT1 p.Asp42= (c.126T>C) pathogenic?

POT1 p.Asp42= (c.126T>C) is classified Likely benign in POT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-31). No allele count reported in gnomAD v4.1 (AN 1,575,176); Associated with tumor predisposition syndrome 3.

What condition is associated with POT1 p.Asp42= (c.126T>C)?

POT1 p.Asp42= (c.126T>C) is associated with tumor predisposition syndrome 3 (ClinVar).

How common is POT1 p.Asp42= (c.126T>C) in the general population?

POT1 p.Asp42= (c.126T>C) is no allele count reported in gnomAD v4.1 (AN 1,575,176) (gnomAD).

POT1 p.Asp42=

c.126T>C · rs1554429221 · VCV1528711

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,575,176)

Conditions

tumor predisposition syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	17.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,575,176). 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.Asp42=
Coding: c.126T>C
MANE Select: NM_015450
dbSNP: rs1554429221
Type: single nucleotide variant
Location: chr7:124871040 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB
Residue 42: the 'dna-binding' region; 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.Asp42Glu Pathogenic/Likely pathogenic ★★ same residue
POT1 p.Asp42Asn Uncertain significance ★★ ⚠ same residue
POT1 p.Asp42Gly Uncertain significance ★★ ⚠ same residue
POT1 p.Asp42Val 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

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-asp42 (accessed [today's date]).

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