Is CHKB c.736+2T>C pathogenic?

CHKB c.736+2T>C is classified Likely pathogenic in CHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2016-09-01). Very rare (popmax 0.00223%, eas).

How common is CHKB c.736+2T>C in the general population?

CHKB c.736+2T>C is very rare (popmax 0.00223%, eas) (gnomAD).

CHKB c.736+2T>C

rs776158594 · VCV430310

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.60	donor loss · deltas
Pangolin	Δ0.55	loss · gain 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Non-coding constraint	Z 2.30	1 kb window · o/e 0.85 · regional · uncalibrated
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,894 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,804 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,894
European (non-Finnish)	0.000169%	590,009

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: CHKB
Coding: c.736+2T>C
MANE Select: NM_005198
dbSNP: rs776158594
Type: single nucleotide variant
Location: chr22:50580356 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 3 PDB

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

Similar variants

CHKB p.Gln51Ter Pathogenic/Likely pathogenic ★★ same type
CHKB c.*208T>G Uncertain significance ★★ same type
CHKB p.Ala361Val Uncertain significance ★★ ⚠ same type
CHKB p.Arg344Trp Uncertain significance ★★ ⚠ same type
CHKB p.Arg62Cys Uncertain significance ★★ ⚠ same type
CHKB p.Gln309Glu Uncertain significance ★★ ⚠ same type
CHKB p.Glu214Asp Uncertain significance ★★ ⚠ same type
CHKB p.Glu336Lys 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/chkb-c-736-plus-2t-c (accessed [today's date]).

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