Is CTSO p.Met101Val (c.301A>G) pathogenic?

CTSO p.Met101Val (c.301A>G) is classified Uncertain significance in CTSO (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely benign (0.0575); Very rare (popmax 0.00875%, amr).

How common is CTSO p.Met101Val (c.301A>G) in the general population?

CTSO p.Met101Val (c.301A>G) is very rare (popmax 0.00875%, amr) (gnomAD).

What do computational predictors say about CTSO p.Met101Val (c.301A>G)?

AlphaMissense predicts likely benign (score 0.0575) — an in-silico prediction, not a clinical call.

CTSO p.Met101Val

c.301A>G · rs747051008 · VCV2355030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0575 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00875%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0575	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -5.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.051	GERP -0.013
Overall
CADD	2.387	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00875% Admixed American · 5/57,116 alleles

Filtering AF 0.00344% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00363% 58/1,596,854 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00875%	11,423
European (non-Finnish)	0.00443%	22,550
Remaining individualsnot grpmax-eligible	0.00162%	61,706

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.Met101Val
Coding: c.301A>G
MANE Select: NM_000396 · reported on NM_001334
dbSNP: rs747051008
Type: single nucleotide variant
Location: chr4:155942400 (GRCh38)
Structure: AlphaFold pLDDT 94.89 · 70 PDB

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

Similar variants

CTSK p.Arg101His Uncertain significance ★ ⚠ same residue
CTSK p.Arg101Leu Uncertain significance ★ ⚠ 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

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-met101val (accessed [today's date]).

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