Is CTSO p.Gly173Val (c.518G>T) pathogenic?

CTSO p.Gly173Val (c.518G>T) is classified Uncertain significance in CTSO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely pathogenic (0.9599); Ultra-rare (popmax 0.0653%, afr).

How common is CTSO p.Gly173Val (c.518G>T) in the general population?

CTSO p.Gly173Val (c.518G>T) is ultra-rare (popmax 0.0653%, afr) (gnomAD).

What do computational predictors say about CTSO p.Gly173Val (c.518G>T)?

AlphaMissense predicts likely pathogenic (score 0.9599) — an in-silico prediction, not a clinical call.

CTSO p.Gly173Val

c.518G>T · rs143745102 · VCV3078787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9599 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0653%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9599	likely pathogenic
REVEL	0.963	strongly pathogenic-leaning
SaProt	LLR -15.27	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 5.9	GERP 2.6, phastCons 1
Overall
CADD	27.7	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

Grpmax group 0.0653% African / African-American · 49/75,034 alleles

Filtering AF 0.0507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0455%

Overall 0.00322% 52/1,613,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0653%	1,531
Admixed American	0.00333%	30,008
Remaining individualsnot grpmax-eligible	0.0016%	62,498

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: CTSO
Protein: p.Gly173Val
Coding: c.518G>T
MANE Select: NM_000396 · reported on NM_001334
dbSNP: rs143745102
Type: single nucleotide variant
Location: chr4:155939405 (GRCh38)
Structure: AlphaFold pLDDT 94.89 · 70 PDB
Residue 173: a β-strand; a disulfide bond

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

Similar variants

CTSK p.Glu173Asp Likely benign ★ same residue
CTSK c.121-1G>A Pathogenic/Likely pathogenic ★★ same type
CTSK c.121-2A>G Pathogenic/Likely pathogenic ★★ same type
CTSK c.244-29A>G Pathogenic/Likely pathogenic ★★ same type
CTSK c.244-2A>C Likely pathogenic ★★ same type
CTSK c.400-1G>C Likely pathogenic ★★ same type
CTSK c.784+1G>A Likely pathogenic ★★ same type
CTSK p.Ala277Val 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/ctso-p-gly173val (accessed [today's date]).

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