Is CTSB p.Ser144Arg (c.432C>A) pathogenic?

CTSB p.Ser144Arg (c.432C>A) is classified Uncertain significance in CTSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.183); Absent from gnomAD v4.1.

How common is CTSB p.Ser144Arg (c.432C>A) in the general population?

CTSB p.Ser144Arg (c.432C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSB p.Ser144Arg (c.432C>A)?

AlphaMissense predicts likely benign (score 0.183) — an in-silico prediction, not a clinical call.

CTSB p.Ser144Arg

c.432C>A · VCV4235830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.183 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.183	likely benign
REVEL	0.516	indeterminate
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.76 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.002	GERP -0.85
Regional constraint	o/e 1.73	unconstrained · MANE · 8,326 bp · p 8.5e-54 · regional, not allelic
Overall
CADD	8.195	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTSB
Protein: p.Ser144Arg
Coding: c.432C>A
MANE Select: NM_001908
Type: single nucleotide variant
Location: chr8:11849060 (GRCh38)
Gene constraint: LOEUF 1.756 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.95 · 21 PDB
Residue 144: a disulfide bond; an α-helix

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

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-ser144arg (accessed [today's date]).

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