Is CTNS p.Ala172Ser (c.514G>T) pathogenic?

CTNS p.Ala172Ser (c.514G>T) is classified Uncertain significance in CTNS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-21). AlphaMissense: likely benign (0.1466); Very rare (popmax 0.00169%, amr); Associated with Inborn genetic diseases.

What condition is associated with CTNS p.Ala172Ser (c.514G>T)?

CTNS p.Ala172Ser (c.514G>T) is associated with Inborn genetic diseases, ocular cystinosis, juvenile nephropathic cystinosis (ClinVar).

How common is CTNS p.Ala172Ser (c.514G>T) in the general population?

CTNS p.Ala172Ser (c.514G>T) is very rare (popmax 0.00169%, amr) (gnomAD).

What do computational predictors say about CTNS p.Ala172Ser (c.514G>T)?

AlphaMissense predicts likely benign (score 0.1466) — an in-silico prediction, not a clinical call.

CTNS p.Ala172Ser

c.514G>T · rs907916051 · VCV2160029

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1466 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1466	likely benign
REVEL	0.787	moderately pathogenic-leaning
SaProt	LLR -7.45	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.7	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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% Admixed American · 1/59,242 alleles

Overall 0.000186% 3/1,608,598 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00169%	59,242
Remaining individualsnot grpmax-eligible	0.0016%	62,370
African / African-American	0.00137%	72,728

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.Ala172Ser
Coding: c.514G>T
MANE Select: NM_004937
dbSNP: rs907916051
Type: single nucleotide variant
Location: chr17:3656539 (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 172: an α-helix; the pq-loop 1 domain

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 p.Ala172= Benign/Likely benign ★★ same residue
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

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-ala172ser (accessed [today's date]).

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