Is CTSE p.Pro213Gln (c.638C>A) pathogenic?

CTSE p.Pro213Gln (c.638C>A) is classified Uncertain significance in CTSE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: ambiguous (0.3902); Absent from gnomAD v4.1.

How common is CTSE p.Pro213Gln (c.638C>A) in the general population?

CTSE p.Pro213Gln (c.638C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSE p.Pro213Gln (c.638C>A)?

AlphaMissense predicts ambiguous (score 0.3902) — an in-silico prediction, not a clinical call.

CTSE p.Pro213Gln

c.638C>A · VCV4008165

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3902 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3902	ambiguous
SaProt	LLR -10.83	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 0.81, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 14 kb · p 0.083 · regional, not allelic
Overall
CADD	23.7	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: CTSE
Protein: p.Pro213Gln
Coding: c.638C>A
MANE Select: NM_001910
Type: single nucleotide variant
Location: chr1:206015955 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.31 · 1 PDB
Residue 213: a β-strand; the peptidase a1 domain

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

Similar variants

CTSE p.Pro213Leu Uncertain significance ★ ⚠ same residue
CTSE p.Gly80Asp Uncertain significance ★★ ⚠ same type
CTSE p.Ala206Thr Uncertain significance ★ ⚠ same type
CTSE p.Ala259Pro Uncertain significance ★ ⚠ same type
CTSE p.Arg23Ser Uncertain significance ★ ⚠ same type
CTSE p.Arg23Trp Uncertain significance ★ ⚠ same type
CTSE p.Arg28Ser Uncertain significance ★ ⚠ same type
CTSE p.Arg37Gln Uncertain significance ★ ⚠ 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/ctse-p-pro213gln (accessed [today's date]).

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