Is CTSC p.Leu267Pro (c.800T>C) pathogenic?

CTSC p.Leu267Pro (c.800T>C) is classified Uncertain significance in CTSC (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-10). AlphaMissense: likely pathogenic (0.9429); Absent from gnomAD v4.1.

How common is CTSC p.Leu267Pro (c.800T>C) in the general population?

CTSC p.Leu267Pro (c.800T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSC p.Leu267Pro (c.800T>C)?

AlphaMissense predicts likely pathogenic (score 0.9429) — an in-silico prediction, not a clinical call.

CTSC p.Leu267Pro

c.800T>C · rs2134765897 · VCV1311590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9429 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9429	likely pathogenic · top 5% in CTSC
REVEL	0.941	strongly pathogenic-leaning
SaProt	LLR -15.26	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 44 kb · p 0.26 · regional, not allelic
Overall
CADD	29.8	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

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: CTSC
Protein: p.Leu267Pro
Coding: c.800T>C
MANE Select: NM_001814
dbSNP: rs2134765897
Type: single nucleotide variant
Location: chr11:88296222 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 18 PDB
Residue 267: a disulfide bond; an α-helix

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

Similar variants

CTSC c.319-1G>A Pathogenic ★★ same type
CTSC c.757+1G>T Likely pathogenic ★★ same type
CTSC c.-55C>A Pathogenic ★★ same type
CTSC p.Arg210Ter Pathogenic ★★ same type
CTSC p.Arg250Ter Pathogenic/Likely pathogenic ★★ same type
CTSC p.Arg272His Pathogenic/Likely pathogenic ★★ ⚠ same type
CTSC p.Arg272Pro Pathogenic/Likely pathogenic ★★ same type
CTSC p.Arg339Cys 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/ctsc-p-leu267pro (accessed [today's date]).

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