Is CTSD p.Thr155= (c.465T>C) pathogenic?

CTSD p.Thr155= (c.465T>C) is classified Benign in CTSD (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 13.9%, mid) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with CTSD p.Thr155= (c.465T>C)?

CTSD p.Thr155= (c.465T>C) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 10, neuronal ceroid lipofuscinosis (ClinVar).

CTSD p.Thr155=

Q: How common is CTSD p.Thr155= (c.465T>C) in the general population?

CTSD p.Thr155= (c.465T>C) is common (popmax 13.9%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.465T>C · rs11555039 · VCV128876

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 13.9%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.052	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.2	GERP -2.9
Overall
CADD	0.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.9% Middle Eastern · 843/6,050 alleles

Filtering AF 13.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.8%

Overall 8.3% 133,452/1,606,950 alleles · common exomes 120,716/1,454,746 · genomes 12,736/152,204 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	13.9%	7
Ashkenazi Jewishnot grpmax-eligible	10.5%	10
African / African-American	9.9%	10
South Asian	9.73%	10
Remaining individualsnot grpmax-eligible	8.8%	11
European (non-Finnish)	8.51%	12
Admixed American	5.95%	17
Finnishnot grpmax-eligible	5.05%	20
East Asian	2.5%	40
Amishnot grpmax-eligible	2.3%	43

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.Thr155=
Coding: c.465T>C
MANE Select: NM_001909
dbSNP: rs11555039
Type: single nucleotide variant
Location: chr11:1758975 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 155: a β-strand; the peptidase a1 domain

Full CTSD 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

Also linked: neuronal ceroid lipofuscinosis 10 neuronal ceroid lipofuscinosis

Similar variants

CTSD p.Thr155Ser Uncertain significance ★ ⚠ same residue
CTSD p.Thr155fs Pathogenic ★ 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 c.*210C>G Uncertain significance ★★ same condition
CTSD p.Ala10Ser Uncertain significance ★★ ⚠ same condition
CTSD p.Ala116Thr 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-thr155 (accessed [today's date]).

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