Is CTSC p.Val56Ile (c.166G>A) pathogenic?

CTSC p.Val56Ile (c.166G>A) is classified Uncertain significance in CTSC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). AlphaMissense: likely benign (0.0752); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CTSC p.Val56Ile (c.166G>A)?

CTSC p.Val56Ile (c.166G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CTSC p.Val56Ile (c.166G>A) in the general population?

CTSC p.Val56Ile (c.166G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSC p.Val56Ile (c.166G>A)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

CTSC p.Val56Ile

c.166G>A · rs927516888 · VCV2610220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,572,886)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.21	donor loss, 40 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 3.2	GERP 0.54, phastCons 0.4
Regional constraint	o/e 1.05	unconstrained · MANE · 44 kb · p 0.26 · regional, not allelic
Overall
CADD	18.13	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

No allele count reported in gnomAD v4.1 (AN 1,572,886). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CTSC
Protein: p.Val56Ile
Coding: c.166G>A
MANE Select: NM_001814
dbSNP: rs927516888
Type: single nucleotide variant
Location: chr11:88337507 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 18 PDB
Residue 56: 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.Val56= Likely benign ★★ same residue
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

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-val56ile (accessed [today's date]).

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