Is CTSD p.Ala58Val (c.173C>T) pathogenic?

CTSD p.Ala58Val (c.173C>T) is classified Benign/Likely benign in CTSD (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.079); Common (popmax 12.6%, mid) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with CTSD p.Ala58Val (c.173C>T)?

CTSD p.Ala58Val (c.173C>T) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 10, neuronal ceroid lipofuscinosis (ClinVar).

What do computational predictors say about CTSD p.Ala58Val (c.173C>T)?

AlphaMissense predicts likely benign (score 0.079) — an in-silico prediction, not a clinical call.

CTSD p.Ala58Val

Q: How common is CTSD p.Ala58Val (c.173C>T) in the general population?

CTSD p.Ala58Val (c.173C>T) is common (popmax 12.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.173C>T · rs17571 · VCV128873

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.079 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 12.6%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.079	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.17	GERP -1.9
Regional constraint	o/e 0.87	unconstrained · MANE · 10 kb · p 0.0029 · regional, not allelic
Overall
CADD	9.723	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.6% Middle Eastern · 761/6,062 alleles

Filtering AF 11.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.5%

Overall 7.8% 125,912/1,613,604 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	12.6%	8
South Asian	9.48%	11
Ashkenazi Jewishnot grpmax-eligible	8.86%	11
European (non-Finnish)	8.4%	12
Remaining individualsnot grpmax-eligible	8.08%	12
Admixed American	5.36%	19
Finnishnot grpmax-eligible	5.05%	20
African / African-American	2.95%	34
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.Ala58Val
Coding: c.173C>T
dbSNP: rs17571
Type: single nucleotide variant
Location: chr11:1761364 (GRCh38)

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

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-ala58val (accessed [today's date]).

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