Is CTSA p.Leu236Pro (c.707T>C) pathogenic?

CTSA p.Leu236Pro (c.707T>C) is classified Pathogenic in CTSA (ClinVar, No assertion criteria, 1 submitter; last evaluated 1991-12-01). AlphaMissense: likely pathogenic (0.9942); Absent from gnomAD v4.1; Associated with GALACTOSIALIDOSIS, EARLY INFANTILE.

What condition is associated with CTSA p.Leu236Pro (c.707T>C)?

CTSA p.Leu236Pro (c.707T>C) is associated with GALACTOSIALIDOSIS, EARLY INFANTILE (ClinVar).

How common is CTSA p.Leu236Pro (c.707T>C) in the general population?

CTSA p.Leu236Pro (c.707T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSA p.Leu236Pro (c.707T>C)?

AlphaMissense predicts likely pathogenic (score 0.9942) — an in-silico prediction, not a clinical call.

CTSA p.Leu236Pro

c.707T>C · rs137854546 · VCV384

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9942 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GALACTOSIALIDOSIS, EARLY INFANTILE

Computational evidence

Protein change
AlphaMissense	0.9942	likely pathogenic ✓ concordant with ClinVar · top 2% in CTSA
REVEL	0.826	moderately pathogenic-leaning
SaProt	LLR -14.83	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.22	constrained · MANE · 734 bp · p 0.00024 · regional, not allelic
Overall
CADD	29.7	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

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: CTSA
Protein: p.Leu236Pro
Coding: c.707T>C
MANE Select: NM_000308 · reported on NM_001127695
dbSNP: rs137854546
Type: single nucleotide variant
Location: chr20:45894002 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB
Residue 236: a UniProt-annotated variant site (in gsl); an α-helix; a disulfide bond

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

Disease context

GALACTOSIALIDOSIS, EARLY INFANTILE — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTSA p.Leu236= Likely benign ★ same residue
CTSA c.1-2A>G Pathogenic/Likely pathogenic ★★ same type
CTSA c.358-2A>G Likely pathogenic ★★ same type
CTSA c.601-2A>G Pathogenic/Likely pathogenic ★★ same type
CTSA c.692+3A>G Pathogenic ★★ same type
CTSA c.948+1G>A Likely pathogenic ★★ same type
CTSA p.Arg375Ter Pathogenic/Likely pathogenic ★★ same type
CTSA p.Cys256Ter Pathogenic/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/ctsa-p-leu236pro (accessed [today's date]).

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