Is CST6 p.Val15Asp (c.44T>A) pathogenic?

CST6 p.Val15Asp (c.44T>A) is classified Uncertain significance in CST6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: likely pathogenic (0.651); Very rare (popmax 7.06e-05%).

How common is CST6 p.Val15Asp (c.44T>A) in the general population?

CST6 p.Val15Asp (c.44T>A) is very rare (popmax 7.06e-05%) (gnomAD).

What do computational predictors say about CST6 p.Val15Asp (c.44T>A)?

AlphaMissense predicts likely pathogenic (score 0.651) — an in-silico prediction, not a clinical call.

CST6 p.Val15Asp

c.44T>A · VCV4007743

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.06e-05%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.651	likely pathogenic
REVEL	0.211	benign-leaning
SaProt	LLR -15.04	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.035, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 1,352 bp · p 0.95 · regional, not allelic
Overall
CADD	21.3	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

Grpmax group 7.06e-05%

Overall 7.06e-05% 1/1,415,728 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: CST6
Protein: p.Val15Asp
Coding: c.44T>A
MANE Select: NM_001323
Type: single nucleotide variant
Location: chr11:66012088 (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.Val15Ile Uncertain significance ★ ⚠ 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-val15asp (accessed [today's date]).

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