Is CST7 p.Leu69Ser (c.206T>C) pathogenic?

CST7 p.Leu69Ser (c.206T>C) is classified Uncertain significance in CST7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: ambiguous (0.5559); Absent from gnomAD v4.1.

How common is CST7 p.Leu69Ser (c.206T>C) in the general population?

CST7 p.Leu69Ser (c.206T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CST7 p.Leu69Ser (c.206T>C)?

AlphaMissense predicts ambiguous (score 0.5559) — an in-silico prediction, not a clinical call.

CST7 p.Leu69Ser

c.206T>C · VCV3497977

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5559 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5559	ambiguous
REVEL	0.376	indeterminate
SaProt	LLR -12.81	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 10 kb · p 0.29 · regional, not allelic
Overall
CADD	24.4	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: CST7
Protein: p.Leu69Ser
Coding: c.206T>C
MANE Select: NM_003650
Type: single nucleotide variant
Location: chr20:24957422 (GRCh38)
Gene constraint: LOEUF 1.742 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.78 · 1 PDB
Residue 69: a β-strand

Full CST7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST7 p.Ala9Val Uncertain significance ★ ⚠ same type
CST7 p.Arg33His Uncertain significance ★ ⚠ same type
CST7 p.Arg96Ser Uncertain significance ★ ⚠ same type
CST7 p.Asn61His Uncertain significance ★ ⚠ same type
CST7 p.Cys63Arg Uncertain significance ★ ⚠ same type
CST7 p.Cys99Ser Uncertain significance ★ ⚠ same type
CST7 p.Glu138Gln Uncertain significance ★ ⚠ same type
CST7 p.Glu138Lys 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/cst7-p-leu69ser (accessed [today's date]).

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