Is CTSK p.His276= (c.828T>C) pathogenic?

CTSK p.His276= (c.828T>C) is classified Likely benign in CTSK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-20). Absent from gnomAD v4.1.

How common is CTSK p.His276= (c.828T>C) in the general population?

CTSK p.His276= (c.828T>C) is absent from gnomAD v4.1 (gnomAD).

CTSK p.His276=

c.828T>C · rs2525165595 · VCV2079688

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,312)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.8	GERP -3.4
Overall
CADD	0.423	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,312). 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: CTSK
Protein: p.His276=
Coding: c.828T>C
MANE Select: NM_000396
dbSNP: rs2525165595
Type: single nucleotide variant
Location: chr1:150799230 (GRCh38)
Gene constraint: LOEUF 0.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.89 · 70 PDB
Residue 276: an active site; a β-strand; a disulfide bond

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

Similar variants

CTSK p.His276Arg Likely pathogenic ★ same residue
CTSK p.His276Tyr Likely pathogenic ★ same residue
CTSK p.His276fs Likely pathogenic ★ same residue
CTSK c.121-1G>A Pathogenic/Likely pathogenic ★★ same type
CTSK c.121-2A>G Pathogenic/Likely pathogenic ★★ same type
CTSK c.244-29A>G Pathogenic/Likely pathogenic ★★ same type
CTSK c.244-2A>C Likely pathogenic ★★ same type
CTSK c.400-1G>C Likely pathogenic ★★ 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/ctsk-p-his276 (accessed [today's date]).

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