Is CTSD p.Glu44Asp (c.132G>C) pathogenic?

CTSD p.Glu44Asp (c.132G>C) is classified Uncertain significance in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-08). AlphaMissense: likely benign (0.1261); Very rare (popmax 0.00934%, afr); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Glu44Asp (c.132G>C)?

CTSD p.Glu44Asp (c.132G>C) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSD p.Glu44Asp (c.132G>C) in the general population?

CTSD p.Glu44Asp (c.132G>C) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about CTSD p.Glu44Asp (c.132G>C)?

AlphaMissense predicts likely benign (score 0.1261) — an in-silico prediction, not a clinical call.

CTSD p.Glu44Asp

c.132G>C · rs985529538 · VCV2194432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1261 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.1261	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -7.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.5	GERP -2
Regional constraint	o/e 0.87	unconstrained · MANE · 10 kb · p 0.0029 · regional, not allelic
Overall
CADD	3.869	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 0.00934% African / African-American · 7/74,934 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000434% 7/1,613,756 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.Glu44Asp
Coding: c.132G>C
dbSNP: rs985529538
Type: single nucleotide variant
Location: chr11:1761405 (GRCh38)

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

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-glu44asp (accessed [today's date]).

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