Is POT1 p.Ala230= (c.690A>G) pathogenic?

POT1 p.Ala230= (c.690A>G) is classified Likely benign in POT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-25). No allele count reported in gnomAD v4.1 (AN 1,606,554); Associated with hereditary neoplastic syndrome.

What condition is associated with POT1 p.Ala230= (c.690A>G)?

POT1 p.Ala230= (c.690A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is POT1 p.Ala230= (c.690A>G) in the general population?

POT1 p.Ala230= (c.690A>G) is no allele count reported in gnomAD v4.1 (AN 1,606,554) (gnomAD).

POT1 p.Ala230=

c.690A>G · rs2485462882 · VCV1756095

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 1,606,554)

Conditions

hereditary neoplastic syndrome

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 · T>A here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.67	GERP 0.73, phastCons 0.016
Overall
CADD	8.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,606,554). 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.Ala230=
Coding: c.690A>G
MANE Select: NM_015450
dbSNP: rs2485462882
Type: single nucleotide variant
Location: chr7:124858969 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 87.63 · 14 PDB
Residue 230: an α-helix

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.Ala230Thr Uncertain significance ★★ ⚠ same residue
POT1 p.Ala230Ser 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

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-ala230 (accessed [today's date]).

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