Is CTSC p.Glu161Asp (c.483A>C) pathogenic?

CTSC p.Glu161Asp (c.483A>C) is classified Uncertain significance in CTSC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.1025); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTSC p.Glu161Asp (c.483A>C)?

CTSC p.Glu161Asp (c.483A>C) is associated with Inborn genetic diseases (ClinVar).

How common is CTSC p.Glu161Asp (c.483A>C) in the general population?

CTSC p.Glu161Asp (c.483A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CTSC p.Glu161Asp (c.483A>C)?

AlphaMissense predicts likely benign (score 0.1025) — an in-silico prediction, not a clinical call.

CTSC p.Glu161Asp

c.483A>C · VCV4008146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1025 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1025	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -6.88	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 1.7	GERP -0.81, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 44 kb · p 0.26 · regional, not allelic
Overall
CADD	15.76	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

Grpmax group 0.00133% African / African-American · 1/74,930 alleles

Overall 0.000657% 1/152,236 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: CTSC
Protein: p.Glu161Asp
Coding: c.483A>C
MANE Select: NM_001814
Type: single nucleotide variant
Location: chr11:88312390 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 18 PDB

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

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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-glu161asp (accessed [today's date]).

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