Is CHEK2 p.Asp162fs (c.480_483dup) pathogenic?

CHEK2 p.Asp162fs (c.480483dup) is classified Pathogenic in CHEK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-06-26). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with CHEK2 p.Asp162fs (c.480_483dup)?

CHEK2 p.Asp162fs (c.480_483dup) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is CHEK2 p.Asp162fs (c.480_483dup) in the general population?

CHEK2 p.Asp162fs (c.480_483dup) is no gnomAD frequency available for this variant (gnomAD).

CHEK2 p.Asp162fs

c.480_483dup · rs864622453 · VCV220278

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: CHEK2
Protein: p.Asp162fs
Coding: c.480_483dup
MANE Select: NM_007194
dbSNP: rs864622453
Type: Duplication
Location: chr22:28725085 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 162: the fha domain; a β-strand

Full CHEK2 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

Also linked: hereditary breast carcinoma

Similar variants

CHEK2 p.Asp162Tyr Uncertain significance ★★ ⚠ same residue
CHEK2 p.Asp162Val Uncertain significance ★★ ⚠ same residue
CHEK2 p.Asp162Asn Uncertain significance ★ ⚠ same residue
CHEK2 p.Asp162Glu Uncertain significance ★ ⚠ same residue
CHEK2 p.Asp162Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
CHEK2 p.Asp162= Benign ★ same residue
CHEK2 p.Arg431Ter Pathogenic/Likely pathogenic ★★ same condition
CHEK2 p.Asp203Ter 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/chek2-p-asp162fs (accessed [today's date]).

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