Is CTSE p.Ser229Asn (c.686G>A) pathogenic?

CTSE p.Ser229Asn (c.686G>A) is classified Uncertain significance in CTSE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). AlphaMissense: likely pathogenic (0.6933); Very rare (popmax 8.48e-05%, nfe).

How common is CTSE p.Ser229Asn (c.686G>A) in the general population?

CTSE p.Ser229Asn (c.686G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CTSE p.Ser229Asn (c.686G>A)?

AlphaMissense predicts likely pathogenic (score 0.6933) — an in-silico prediction, not a clinical call.

CTSE p.Ser229Asn

c.686G>A · VCV3837318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6933 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.6933	likely pathogenic
SaProt	LLR -9.99	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.9, phastCons 0.99
Regional constraint	o/e 1.08	unconstrained · MANE · 14 kb · p 0.083 · 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 8.48e-05% European (non-Finnish) · 1/1,179,848 alleles

Overall 6.84e-05% 1/1,461,698 alleles · very rare

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: CTSE
Protein: p.Ser229Asn
Coding: c.686G>A
MANE Select: NM_001910
Type: single nucleotide variant
Location: chr1:206013871 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.31 · 1 PDB
Residue 229: the peptidase a1 domain

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

Similar variants

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
CTSE p.Arg37Trp 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-ser229asn (accessed [today's date]).

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