Is CTNS p.Tyr173His (c.517T>C) pathogenic?

CTNS p.Tyr173His (c.517T>C) is classified Likely pathogenic in CTNS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-14). AlphaMissense: likely pathogenic (0.9608); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Tyr173His (c.517T>C)?

CTNS p.Tyr173His (c.517T>C) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Tyr173His (c.517T>C) in the general population?

CTNS p.Tyr173His (c.517T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTNS p.Tyr173His (c.517T>C)?

AlphaMissense predicts likely pathogenic (score 0.9608) — an in-silico prediction, not a clinical call.

CTNS p.Tyr173His

c.517T>C · rs2076151594 · VCV2925594

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9608 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9608	likely pathogenic ✓ concordant with ClinVar
REVEL	0.943	strongly pathogenic-leaning
SaProt	LLR -12.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.4 · regional, not allelic
Overall
CADD	29.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTNS
Protein: p.Tyr173His
Coding: c.517T>C
dbSNP: rs2076151594
Type: single nucleotide variant
Location: chr17:3656542 (GRCh38)

Full CTNS 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: ocular cystinosis juvenile nephropathic cystinosis nephropathic cystinosis

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/ctns-p-tyr173his (accessed [today's date]).

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