Is CTSD p.Ile191= (c.573C>T) pathogenic?

CTSD p.Ile191= (c.573C>T) is classified Likely benign in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-16). Very rare (popmax 0.000593%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Ile191= (c.573C>T)?

CTSD p.Ile191= (c.573C>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSD p.Ile191= (c.573C>T) in the general population?

CTSD p.Ile191= (c.573C>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

CTSD p.Ile191=

c.573C>T · rs1165243731 · VCV2194027

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.014	strongly benign-leaning
Splicing
SpliceAI	Δ0.56	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -3	GERP -3.7
Overall
CADD	18.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,180,022 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,992 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: CTSD
Protein: p.Ile191=
Coding: c.573C>T
MANE Select: NM_001909
dbSNP: rs1165243731
Type: single nucleotide variant
Location: chr11:1757455 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 191: a turn; the peptidase a1 domain

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

Disease context

neuronal ceroid lipofuscinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTSD p.Ile191Val Uncertain significance ★ ⚠ same residue
CTSD c.228+1G>A Likely pathogenic ★★ same condition
CTSD p.Glu82Ter Pathogenic/Likely pathogenic ★★ same condition
CTSD c.828-3C>A Uncertain significance ★★ same condition
CTSD p.Ala10Ser Uncertain significance ★★ ⚠ same condition
CTSD p.Ala18Pro Uncertain significance ★★ ⚠ same condition
CTSD p.Ala18Thr Uncertain significance ★★ ⚠ same condition
CTSD p.Ala239Val 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/ctsd-p-ile191 (accessed [today's date]).

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