Is CTSE p.Trp103Cys (c.309G>C) pathogenic?

CTSE p.Trp103Cys (c.309G>C) is classified Uncertain significance in CTSE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely pathogenic (0.9972); Rare (popmax 0.648%, afr).

How common is CTSE p.Trp103Cys (c.309G>C) in the general population?

CTSE p.Trp103Cys (c.309G>C) is rare (popmax 0.648%, afr) (gnomAD).

What do computational predictors say about CTSE p.Trp103Cys (c.309G>C)?

AlphaMissense predicts likely pathogenic (score 0.9972) — an in-silico prediction, not a clinical call.

CTSE p.Trp103Cys

c.309G>C · VCV4235852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9972 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.648%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.9972	likely pathogenic · top 1% in CTSE
SaProt	LLR -11.91	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 14 kb · p 0.083 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.648% African / African-American · 486/75,012 alleles

Filtering AF 0.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.581%

Overall 0.0419% 676/1,612,414 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.648%	154
Admixed American	0.0534%	1,873
Remaining individualsnot grpmax-eligible	0.0368%	2,715
European (non-Finnish)	0.0112%	8,931
Finnishnot grpmax-eligible	0.0047%	21,274

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.Trp103Cys
Coding: c.309G>C
MANE Select: NM_001910
Type: single nucleotide variant
Location: chr1:206022184 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.31 · 1 PDB
Residue 103: 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.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-trp103cys (accessed [today's date]).

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