Is CHEK2 p.Val511fs (c.1531del) pathogenic?

CHEK2 p.Val511fs (c.1531del) is classified Likely pathogenic in CHEK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-28). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with CHEK2 p.Val511fs (c.1531del)?

CHEK2 p.Val511fs (c.1531del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is CHEK2 p.Val511fs (c.1531del) in the general population?

CHEK2 p.Val511fs (c.1531del) is absent from gnomAD (gnomAD).

CHEK2 p.Val511fs

c.1531del · rs2145748375 · VCV1692941

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (14 of 15, 11 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.73	GERP 1.8
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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.Val511fs
Coding: c.1531del
MANE Select: NM_007194
dbSNP: rs2145748375
Type: Deletion
Location: chr22:28689146 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 511: the 'disordered' region

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

Similar variants

CHEK2 p.Val511Phe Uncertain significance ★★ ⚠ same residue
CHEK2 p.Val511= Conflicting classifications of pathogenicity ★ same residue
CHEK2 p.Val511_Leu512insTer Likely pathogenic ★ same residue
CHEK2 c.1096-3_1098del Likely pathogenic ★★ same condition
CHEK2 c.1375+1_1375+2del Likely pathogenic ★★ same condition
CHEK2 c.1375+1del Likely pathogenic ★★ same condition
CHEK2 c.1543-11_1543-2del Likely pathogenic ★★ same condition
CHEK2 c.319+1del 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-val511fs (accessed [today's date]).

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