Is CTNS p.Asp305Val (c.914A>T) pathogenic?

CTNS p.Asp305Val (c.914A>T) is classified Uncertain significance in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). AlphaMissense: likely pathogenic (0.9947); Absent from gnomAD v4.1.

How common is CTNS p.Asp305Val (c.914A>T) in the general population?

CTNS p.Asp305Val (c.914A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTNS p.Asp305Val (c.914A>T)?

AlphaMissense predicts likely pathogenic (score 0.9947) — an in-silico prediction, not a clinical call.

CTNS p.Asp305Val

c.914A>T · rs1263951539 · VCV3251333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9947 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9947	likely pathogenic · top 1% in CTNS
REVEL	0.994	strongly pathogenic-leaning
SaProt	LLR -12.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, 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.Asp305Val
Coding: c.914A>T
MANE Select: NM_004937
dbSNP: rs1263951539
Type: single nucleotide variant
Location: chr17:3659919 (GRCh38)
Gene constraint: LOEUF 0.754 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.27 · 6 PDB
Residue 305: an α-helix; the pq-loop 2 domain; a binding site; a UniProt-annotated variant site (in ctns); a UniProt-annotated variant site (in ctns; abolished cystine transport)

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

Similar variants

CTNS p.Asp305Gly Uncertain significance ★ ⚠ same residue
CTNS c.140+1G>C Likely pathogenic ★★ same type
CTNS c.140+1G>T Pathogenic/Likely pathogenic ★★ same type
CTNS c.140+2T>C Pathogenic/Likely pathogenic ★★ same type
CTNS c.141-1G>A Pathogenic/Likely pathogenic ★★ same type
CTNS c.141-24T>C Pathogenic ★★ same type
CTNS c.225+3A>T Pathogenic/Likely pathogenic ★★ same type
CTNS c.225+5G>A Likely pathogenic ★★ same type

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-asp305val (accessed [today's date]).

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