Is CTSB p.Glu157= (c.471A>G) pathogenic?

CTSB p.Glu157= (c.471A>G) is classified Likely benign in CTSB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-11). Ultra-rare (popmax 0.0533%, afr); Associated with CTSB-related disorder.

What condition is associated with CTSB p.Glu157= (c.471A>G)?

CTSB p.Glu157= (c.471A>G) is associated with CTSB-related disorder (ClinVar).

How common is CTSB p.Glu157= (c.471A>G) in the general population?

CTSB p.Glu157= (c.471A>G) is ultra-rare (popmax 0.0533%, afr) (gnomAD).

CTSB p.Glu157=

c.471A>G · rs376137412 · VCV3058284

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, afr)

Conditions

CTSB-related disorder

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 0.085	GERP -3.1, phastCons 0.46
Overall
CADD	5.458	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0533% African / African-American · 40/75,054 alleles

Filtering AF 0.0401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0356%

Overall 0.00266% 43/1,614,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0533%	1,876
Admixed American	0.00167%	60,028
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	8.47e-05%	1,180,002

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: CTSB
Protein: p.Glu157=
Coding: c.471A>G
MANE Select: NM_001908
dbSNP: rs376137412
Type: single nucleotide variant
Location: chr8:11848128 (GRCh38)
Gene constraint: LOEUF 1.756 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.95 · 21 PDB
Residue 157: a disulfide bond; an α-helix

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

Disease context

CTSB-related disorder

Similar variants

CTSB p.Arg331Pro Uncertain significance ★★ ⚠ same type
CTSB p.Asp333Asn Uncertain significance ★★ ⚠ same type
CTSB p.Lys220Glu Uncertain significance ★★ ⚠ same type
CTSB p.Met73Thr Uncertain significance ★★ ⚠ same type
CTSB p.Thr332Ala Uncertain significance ★★ ⚠ same type
CTSB c.327+20C>T Benign ★★ same type
CTSB c.446+9G>C Benign ★★ same type
CTSB c.447-16G>C Benign ★★ 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/ctsb-p-glu157 (accessed [today's date]).

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