Is CTSO p.Val248Met (c.742G>A) pathogenic?

CTSO p.Val248Met (c.742G>A) is classified Uncertain significance in CTSO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.1182); Absent from gnomAD v4.1.

How common is CTSO p.Val248Met (c.742G>A) in the general population?

CTSO p.Val248Met (c.742G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSO p.Val248Met (c.742G>A)?

AlphaMissense predicts likely benign (score 0.1182) — an in-silico prediction, not a clinical call.

CTSO p.Val248Met

c.742G>A · VCV3270235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1182 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1182	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -7.39	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 0.12	GERP 0.7, phastCons 0.003
Overall
CADD	18.42	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTSO
Protein: p.Val248Met
Coding: c.742G>A
MANE Select: NM_000396 · reported on NM_001334
Type: single nucleotide variant
Location: chr4:155929638 (GRCh38)
Structure: AlphaFold pLDDT 94.89 · 70 PDB
Residue 248: a β-strand

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

Similar variants

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
CTSK p.Arg122Ter Pathogenic/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-val248met (accessed [today's date]).

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