Is CHEK2 p.Phe238= (c.714C>T) pathogenic?

CHEK2 p.Phe238= (c.714C>T) is classified Benign/Likely benign in CHEK2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0112%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with CHEK2 p.Phe238= (c.714C>T)?

CHEK2 p.Phe238= (c.714C>T) is associated with hereditary neoplastic syndrome, breast cancer, hereditary breast carcinoma (ClinVar).

How common is CHEK2 p.Phe238= (c.714C>T) in the general population?

CHEK2 p.Phe238= (c.714C>T) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

CHEK2 p.Phe238=

c.714C>T · rs864622322 · VCV219950

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.01	GERP -3, phastCons 0.031
Overall
CADD	9.681	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 5/44,840 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00164% 24/1,461,674 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,968
Remaining individualsnot grpmax-eligible	0.0032%	31,246
European (non-Finnish)	0.00144%	69,402

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: CHEK2
Protein: p.Phe238=
Coding: c.714C>T
MANE Select: NM_007194
dbSNP: rs864622322
Type: single nucleotide variant
Location: chr22:28711987 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 238: a β-strand; the protein kinase domain

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: breast cancer hereditary breast carcinoma

Similar variants

CHEK2 p.Phe238Leu Uncertain significance ★★ ⚠ same residue
CHEK2 p.Phe238Ser Uncertain significance ★ ⚠ same residue
CHEK2 c.1008+1G>A Likely pathogenic ★★ same condition
CHEK2 c.1008+1G>T Likely pathogenic ★★ same condition
CHEK2 c.1008+2T>A Likely pathogenic ★★ same condition
CHEK2 c.1008+2T>G Likely pathogenic ★★ same condition
CHEK2 c.1009-1G>A Likely pathogenic ★★ same condition
CHEK2 c.1009-2A>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/chek2-p-phe238 (accessed [today's date]).

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