Is CST6 p.Gln148Pro (c.443A>C) pathogenic?

CST6 p.Gln148Pro (c.443A>C) is classified Likely benign in CST6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.044); Absent from gnomAD v4.1.

How common is CST6 p.Gln148Pro (c.443A>C) in the general population?

CST6 p.Gln148Pro (c.443A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CST6 p.Gln148Pro (c.443A>C)?

AlphaMissense predicts likely benign (score 0.044) — an in-silico prediction, not a clinical call.

CST6 p.Gln148Pro

c.443A>C · VCV4235340

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.044 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.044	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -2.72	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 0.27	GERP -2.9
Regional constraint	o/e 1.00	unconstrained · MANE · 1,352 bp · p 0.95 · regional, not allelic
Overall
CADD	5.492	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: CST6
Protein: p.Gln148Pro
Coding: c.443A>C
MANE Select: NM_001323
Type: single nucleotide variant
Location: chr11:66013393 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.46 · 5 PDB
Residue 148: a β-strand; a UniProt-annotated variant site (in ectd15; loss of cystein protease inhibitory activity toward cathepsin l, cathepsin v and legumain)

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

Similar variants

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
CST6 p.Arg29Gly 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-gln148pro (accessed [today's date]).

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