Is CST9 p.Ala13Ser (c.37G>T) pathogenic?

CST9 p.Ala13Ser (c.37G>T) is classified Uncertain significance in CST9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.1216); Very rare (popmax 0.00833%, amr).

How common is CST9 p.Ala13Ser (c.37G>T) in the general population?

CST9 p.Ala13Ser (c.37G>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CST9 p.Ala13Ser (c.37G>T)?

AlphaMissense predicts likely benign (score 0.1216) — an in-silico prediction, not a clinical call.

CST9 p.Ala13Ser

c.37G>T · rs763090442 · VCV3078425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1216 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1216	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -8.63	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 -1.6	GERP -2.9
Regional constraint	o/e 1.07	unconstrained · MANE · 2,351 bp · p 0.29 · regional, not allelic
Overall
CADD	6.611	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 0.00833% Admixed American · 5/60,030 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.000342% 5/1,461,842 alleles · very rare

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.Ala13Ser
Coding: c.37G>T
MANE Select: NM_001008693
dbSNP: rs763090442
Type: single nucleotide variant
Location: chr20:23605828 (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.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
CST9 p.Asn38His 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-ala13ser (accessed [today's date]).

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