Is CST6 p.Arg3Gly (c.7C>G) pathogenic?

CST6 p.Arg3Gly (c.7C>G) is classified Uncertain significance in CST6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.0893); Absent from gnomAD v4.1.

How common is CST6 p.Arg3Gly (c.7C>G) in the general population?

CST6 p.Arg3Gly (c.7C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CST6 p.Arg3Gly (c.7C>G)?

AlphaMissense predicts likely benign (score 0.0893) — an in-silico prediction, not a clinical call.

CST6 p.Arg3Gly

c.7C>G · rs2495886581 · VCV2491428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0893 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0893	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -8.30	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 1.2	GERP 1.4
Regional constraint	o/e 1.00	unconstrained · MANE · 1,352 bp · p 0.95 · regional, not allelic
Overall
CADD	17.61	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: CST6
Protein: p.Arg3Gly
Coding: c.7C>G
MANE Select: NM_001323
dbSNP: rs2495886581
Type: single nucleotide variant
Location: chr11:66012051 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.46 · 5 PDB

Full CST6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST6 p.Arg3Leu Likely benign ★ same residue
CST6 p.Leu6= Likely benign ★★ same type
CST6 p.Ala21Val Uncertain significance ★ ⚠ same type
CST6 p.Ala54Val Uncertain significance ★ ⚠ same type
CST6 p.Ala55Ser Uncertain significance ★ ⚠ same type
CST6 p.Arg125Cys Uncertain significance ★ ⚠ same type
CST6 p.Arg24Cys Uncertain significance ★ ⚠ same type
CST6 p.Arg24Gly 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/cst6-p-arg3gly (accessed [today's date]).

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