Is CTSB p.Gln334Pro (c.1001A>C) pathogenic?

CTSB p.Gln334Pro (c.1001A>C) is classified Benign in CTSB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely benign (0.1628); Low-frequency (popmax 3.2%, eas).

How common is CTSB p.Gln334Pro (c.1001A>C) in the general population?

CTSB p.Gln334Pro (c.1001A>C) is low-frequency (popmax 3.2%, eas) (gnomAD).

What do computational predictors say about CTSB p.Gln334Pro (c.1001A>C)?

AlphaMissense predicts likely benign (score 0.1628) — an in-silico prediction, not a clinical call.

CTSB p.Gln334Pro

c.1001A>C · rs117613666 · VCV728614

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1628 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.2%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1628	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP 1.9, phastCons 0.67
Regional constraint	o/e 1.73	unconstrained · MANE · 8,326 bp · p 8.5e-54 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.2% East Asian · 1,436/44,888 alleles

Filtering AF 3.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.01%

Overall 0.165% 2,667/1,613,564 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	3.2%	31
Finnishnot grpmax-eligible	1.2%	83
Remaining individualsnot grpmax-eligible	0.213%	470
South Asian	0.154%	650
Middle Eastern	0.0495%	2,021
European (non-Finnish)	0.0154%	6,481
Admixed American	0.005%	20,005
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
African / African-American	0.00267%	37,519

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.Gln334Pro
Coding: c.1001A>C
MANE Select: NM_001908
dbSNP: rs117613666
Type: single nucleotide variant
Location: chr8:11845144 (GRCh38)
Gene constraint: LOEUF 1.756 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.95 · 21 PDB

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

Similar variants

CTSB p.Gln334Glu Uncertain significance ★ ⚠ same residue
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

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-gln334pro (accessed [today's date]).

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