Is CTNS p.Ser154= (c.462T>C) pathogenic?

CTNS p.Ser154= (c.462T>C) is classified Benign in CTNS (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 20.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Ser154= (c.462T>C)?

CTNS p.Ser154= (c.462T>C) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

CTNS p.Ser154=

Q: How common is CTNS p.Ser154= (c.462T>C) in the general population?

CTNS p.Ser154= (c.462T>C) is common (popmax 20.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.462T>C · rs77453839 · VCV257153

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 20.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.55	GERP -3.1, phastCons 0.016
Overall
CADD	4.511	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.9% African / African-American · 13,430/64,360 alleles

Filtering AF 20.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.5%

Overall 1.13% 17,875/1,587,498 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	20.9%	5
South Asian	2.32%	43
Remaining individualsnot grpmax-eligible	1.51%	66
Admixed American	1.25%	80
Middle Eastern	1.06%	94
East Asian	0.125%	803
European (non-Finnish)	0.0522%	1,917
Finnishnot grpmax-eligible	0.00162%	61,654

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.Ser154=
Coding: c.462T>C
dbSNP: rs77453839
Type: single nucleotide variant
Location: chr17:3656487 (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 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-ser154 (accessed [today's date]).

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