Is CST9 p.Val102Ile (c.304G>A) pathogenic?

CST9 p.Val102Ile (c.304G>A) is classified Uncertain significance in CST9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). AlphaMissense: likely benign (0.0776); Very rare (popmax 0.00891%, eas).

How common is CST9 p.Val102Ile (c.304G>A) in the general population?

CST9 p.Val102Ile (c.304G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CST9 p.Val102Ile (c.304G>A)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

CST9 p.Val102Ile

c.304G>A · VCV3269967

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -7.12	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 -4.2	GERP -2.6
Regional constraint	o/e 1.07	unconstrained · MANE · 2,351 bp · p 0.29 · regional, not allelic
Overall
CADD	0.395	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

Grpmax group 0.00891% East Asian · 4/44,902 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00248% 40/1,614,104 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,225
European (non-Finnish)	0.00288%	34,708
African / African-American	0.00267%	37,460

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: CST9
Protein: p.Val102Ile
Coding: c.304G>A
MANE Select: NM_001008693
Type: single nucleotide variant
Location: chr20:23603686 (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-val102ile (accessed [today's date]).

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