Is CTSC p.Val288Leu (c.862G>C) pathogenic?

CTSC p.Val288Leu (c.862G>C) is classified Uncertain significance in CTSC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: ambiguous (0.3801); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CTSC p.Val288Leu (c.862G>C)?

CTSC p.Val288Leu (c.862G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CTSC p.Val288Leu (c.862G>C) in the general population?

CTSC p.Val288Leu (c.862G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSC p.Val288Leu (c.862G>C)?

AlphaMissense predicts ambiguous (score 0.3801) — an in-silico prediction, not a clinical call.

CTSC p.Val288Leu

c.862G>C · VCV4616730

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3801 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3801	ambiguous
REVEL	0.416	indeterminate
SaProt	LLR -8.08	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP -1.1, phastCons 0.97
Regional constraint	o/e 1.05	unconstrained · MANE · 44 kb · p 0.26 · regional, not allelic
Overall
CADD	16.56	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: CTSC
Protein: p.Val288Leu
Coding: c.862G>C
MANE Select: NM_001814
Type: single nucleotide variant
Location: chr11:88296160 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 18 PDB
Residue 288: a disulfide bond; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTSC p.Ala269Val Uncertain significance ★★ ⚠ same condition
CTSC p.Arg442His Uncertain significance ★★ ⚠ same condition
CTSC p.Ile282Val Uncertain significance ★★ ⚠ same condition
CTSC p.Phe439Leu Uncertain significance ★★ ⚠ same condition
CTSC p.Thr188Ala Uncertain significance ★★ ⚠ same condition
CTSC p.Tyr32Cys Uncertain significance ★★ ⚠ same condition
CTSC p.Val22Leu Uncertain significance ★★ ⚠ same condition
CTSC p.Ala154Val Uncertain significance ★ ⚠ same condition

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/ctsc-p-val288leu (accessed [today's date]).

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