Is CTNS p.Ala137Asp (c.410C>A) pathogenic?

CTNS p.Ala137Asp (c.410C>A) is classified Uncertain significance in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). AlphaMissense: likely pathogenic (0.9805); Absent from gnomAD v4.1; Associated with juvenile nephropathic cystinosis.

What condition is associated with CTNS p.Ala137Asp (c.410C>A)?

CTNS p.Ala137Asp (c.410C>A) is associated with juvenile nephropathic cystinosis, ocular cystinosis (ClinVar).

How common is CTNS p.Ala137Asp (c.410C>A) in the general population?

CTNS p.Ala137Asp (c.410C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTNS p.Ala137Asp (c.410C>A)?

AlphaMissense predicts likely pathogenic (score 0.9805) — an in-silico prediction, not a clinical call.

CTNS p.Ala137Asp

c.410C>A · rs1413852868 · VCV1472105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9805 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

juvenile nephropathic cystinosis

Computational evidence

Protein change
AlphaMissense	0.9805	likely pathogenic
REVEL	0.908	moderately pathogenic-leaning
SaProt	LLR -13.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.4 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Ala137Asp
Coding: c.410C>A
dbSNP: rs1413852868
Type: single nucleotide variant
Location: chr17:3655301 (GRCh38)

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

Disease context

juvenile nephropathic cystinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ocular 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-ala137asp (accessed [today's date]).

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