Is CTSB p.Ala241= (c.723C>T) pathogenic?

CTSB p.Ala241= (c.723C>T) is classified Likely benign in CTSB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). Very rare (popmax 0.00329%, sas).

How common is CTSB p.Ala241= (c.723C>T) in the general population?

CTSB p.Ala241= (c.723C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

CTSB p.Ala241=

c.723C>T · rs772885286 · VCV1674087

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

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 -15	GERP -3.4
Overall
CADD	0.068	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,068 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000547% 8/1,461,442 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,356
African / African-American	0.00133%	75,010
European (non-Finnish)	0.000339%	294,906

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.Ala241=
Coding: c.723C>T
MANE Select: NM_001908
dbSNP: rs772885286
Type: single nucleotide variant
Location: chr8:11847122 (GRCh38)
Gene constraint: LOEUF 1.756 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.95 · 21 PDB
Residue 241: an α-helix

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

Similar variants

CTSB p.Ala241Val 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-ala241 (accessed [today's date]).

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