Is CTNS p.Val214= (c.642C>G) pathogenic?

CTNS p.Val214= (c.642C>G) is classified Likely benign in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-21). Very rare (popmax 0.00483%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Val214= (c.642C>G)?

CTNS p.Val214= (c.642C>G) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Val214= (c.642C>G) in the general population?

CTNS p.Val214= (c.642C>G) is very rare (popmax 0.00483%, nfe) (gnomAD).

CTNS p.Val214=

c.642C>G · rs760843675 · VCV1158850

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00483%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.99	GERP -0.77, phastCons 0.45
Overall
CADD	4.286	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00483% European (non-Finnish) · 57/1,180,018 alleles

Filtering AF 0.00377% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00366% 59/1,613,398 alleles · very rare exomes 56/1,461,318 · genomes 3/152,080 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00483%	20,702
African / African-American	0.00267%	37,451

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: CTNS
Protein: p.Val214=
Coding: c.642C>G
MANE Select: NM_004937
dbSNP: rs760843675
Type: single nucleotide variant
Location: chr17:3656756 (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 214: an α-helix

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

Similar variants

CTNS c.140+1G>T Pathogenic/Likely pathogenic ★★ same condition
CTNS c.140+2T>C Pathogenic/Likely pathogenic ★★ same condition
CTNS c.141-1G>A Pathogenic/Likely pathogenic ★★ same condition
CTNS c.141-24T>C Pathogenic ★★ same condition
CTNS c.225+3A>T Pathogenic/Likely pathogenic ★★ same condition
CTNS c.225+5G>A Likely pathogenic ★★ same condition
CTNS c.61+2T>C Likely pathogenic ★★ same condition
CTNS c.61+5G>A Pathogenic/Likely pathogenic ★★ same condition

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-val214 (accessed [today's date]).

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