Is CHEK1 p.Phe300= (c.900C>T) pathogenic?

CHEK1 p.Phe300= (c.900C>T) is classified Likely benign in CHEK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-26). Very rare (popmax 8.48e-05%, nfe).

How common is CHEK1 p.Phe300= (c.900C>T) in the general population?

CHEK1 p.Phe300= (c.900C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CHEK1 p.Phe300=

c.900C>T · rs766554144 · VCV1765460

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 0.42	GERP -1.1, phastCons 0.99
Overall
CADD	8.725	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,904 alleles

Overall 0.000657% 1/152,186 alleles · very rare

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: CHEK1
Protein: p.Phe300=
Coding: c.900C>T
MANE Select: NM_001114122
dbSNP: rs766554144
Type: single nucleotide variant
Location: chr11:125643877 (GRCh38)
Gene constraint: LOEUF 0.831 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.04 · 168 PDB
Residue 300: the 'disordered' region

Full CHEK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHEK1 p.Gln346Ter Likely pathogenic ★★ same type
CHEK1 p.Arg277Gln Uncertain significance ★★ ⚠ same type
CHEK1 p.Arg420= Benign ★★ same type
CHEK1 p.Ile471Val Benign ★★ same type
CHEK1 c.-160C>T Uncertain significance ★ same type
CHEK1 c.-83T>C Uncertain significance ★ same type
CHEK1 p.Ala200Ser Uncertain significance ★ ⚠ same type
CHEK1 p.Ala34Pro Uncertain significance ★ ⚠ same type

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/chek1-p-phe300 (accessed [today's date]).

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