Is CST5 p.Trp128Cys (c.384G>C) pathogenic?

CST5 p.Trp128Cys (c.384G>C) is classified Uncertain significance in CST5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: likely pathogenic (0.9219); Absent from gnomAD v4.1.

How common is CST5 p.Trp128Cys (c.384G>C) in the general population?

CST5 p.Trp128Cys (c.384G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CST5 p.Trp128Cys (c.384G>C)?

AlphaMissense predicts likely pathogenic (score 0.9219) — an in-silico prediction, not a clinical call.

CST5 p.Trp128Cys

c.384G>C · rs2514870459 · VCV2261760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9219 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9219	likely pathogenic · top 1% in CST5
REVEL	0.139	moderately benign-leaning
SaProt	LLR -14.20	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.2, phastCons 0.21
Regional constraint	o/e 1.25	unconstrained · MANE · 3,485 bp · p 0.00076 · regional, not allelic
Overall
CADD	23.2	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: CST5
Protein: p.Trp128Cys
Coding: c.384G>C
MANE Select: NM_001900
dbSNP: rs2514870459
Type: single nucleotide variant
Location: chr20:23876233 (GRCh38)
Gene constraint: LOEUF 1.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.46 · 2 PDB
Residue 128: a turn; a disulfide bond

Full CST5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST5 p.Ala23Thr Uncertain significance ★ ⚠ same type
CST5 p.Ala31Thr Uncertain significance ★ ⚠ same type
CST5 p.Ala36Val Uncertain significance ★ ⚠ same type
CST5 p.Ala51Val Uncertain significance ★ ⚠ same type
CST5 p.Arg140Trp Uncertain significance ★ ⚠ same type
CST5 p.Asn101Ser Uncertain significance ★ ⚠ same type
CST5 p.Asn83His Uncertain significance ★ ⚠ same type
CST5 p.Asp41Gly 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/cst5-p-trp128cys (accessed [today's date]).

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