Is CST9 p.Ile153Phe (c.457A>T) pathogenic?

CST9 p.Ile153Phe (c.457A>T) is classified Uncertain significance in CST9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). AlphaMissense: likely benign (0.0819); Absent from gnomAD v4.1.

How common is CST9 p.Ile153Phe (c.457A>T) in the general population?

CST9 p.Ile153Phe (c.457A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CST9 p.Ile153Phe (c.457A>T)?

AlphaMissense predicts likely benign (score 0.0819) — an in-silico prediction, not a clinical call.

CST9 p.Ile153Phe

c.457A>T · rs2515323549 · VCV3078429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0819 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0819	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -6.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -2.6
Regional constraint	o/e 1.07	unconstrained · MANE · 2,351 bp · p 0.29 · regional, not allelic
Overall
CADD	0.128	PHRED · no single calibrated threshold — expert panels disagree

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

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: CST9
Protein: p.Ile153Phe
Coding: c.457A>T
MANE Select: NM_001008693
dbSNP: rs2515323549
Type: single nucleotide variant
Location: chr20:23603533 (GRCh38)
Gene constraint: LOEUF 1.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.21

Full CST9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST9 p.Ala13Ser Uncertain significance ★ ⚠ same type
CST9 p.Ala9Thr Uncertain significance ★ ⚠ same type
CST9 p.Arg78Ser Uncertain significance ★ ⚠ same type
CST9 p.Arg7Lys Uncertain significance ★ ⚠ same type
CST9 p.Arg99Cys Uncertain significance ★ ⚠ same type
CST9 p.Arg99His Uncertain significance ★ ⚠ same type
CST9 p.Asn123Asp Uncertain significance ★ ⚠ same type
CST9 p.Asn123Ser 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/cst9-p-ile153phe (accessed [today's date]).

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