Is CST9L p.Cys142Trp (c.426C>G) pathogenic?

CST9L p.Cys142Trp (c.426C>G) is classified Uncertain significance in CST9L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: likely pathogenic (0.8442); Absent from gnomAD v4.1.

How common is CST9L p.Cys142Trp (c.426C>G) in the general population?

CST9L p.Cys142Trp (c.426C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CST9L p.Cys142Trp (c.426C>G)?

AlphaMissense predicts likely pathogenic (score 0.8442) — an in-silico prediction, not a clinical call.

CST9L p.Cys142Trp

c.426C>G · VCV4657344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8442 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8442	likely pathogenic · top 5% in CST9L
REVEL	0.189	benign-leaning
SaProt	LLR -13.98	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 0.13	GERP -0.68, phastCons 0.007
Regional constraint	o/e 1.00	unconstrained · MANE · 3,499 bp · p 0.97 · regional, not allelic
Overall
CADD	19.49	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: CST9L
Protein: p.Cys142Trp
Coding: c.426C>G
MANE Select: NM_080610
Type: single nucleotide variant
Location: chr20:23564966 (GRCh38)
Gene constraint: LOEUF 1.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54
Residue 142: a disulfide bond

Full CST9L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST9L p.Cys142Arg Uncertain significance ★ ⚠ same residue
CST9L p.Asp64Tyr Uncertain significance ★ ⚠ same type
CST9L p.Cys37Tyr Uncertain significance ★ ⚠ same type
CST9L p.Gln111Arg Uncertain significance ★ ⚠ same type
CST9L p.Ile73Met Uncertain significance ★ ⚠ same type
CST9L p.Leu17Pro Uncertain significance ★ ⚠ same type
CST9L p.Leu25Pro Uncertain significance ★ ⚠ same type
CST9L p.Leu74Phe 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/cst9l-p-cys142trp (accessed [today's date]).

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