Is CTSS p.Asp120Ala (c.359A>C) pathogenic?

CTSS p.Asp120Ala (c.359A>C) is classified Uncertain significance in CTSS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely pathogenic (0.9198); Absent from gnomAD v4.1.

How common is CTSS p.Asp120Ala (c.359A>C) in the general population?

CTSS p.Asp120Ala (c.359A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSS p.Asp120Ala (c.359A>C)?

AlphaMissense predicts likely pathogenic (score 0.9198) — an in-silico prediction, not a clinical call.

CTSS p.Asp120Ala

c.359A>C · rs2525086584 · VCV2613626

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9198 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9198	likely pathogenic
REVEL	0.762	pathogenic-leaning
SaProt	LLR -18.01	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 32 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	28.1	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: CTSS
Protein: p.Asp120Ala
Coding: c.359A>C
MANE Select: NM_004079
dbSNP: rs2525086584
Type: single nucleotide variant
Location: chr1:150755041 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 94.51 · 62 PDB

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

Similar variants

CTSS p.Val296= Benign ★★ same type
CTSS p.Ala243Thr Uncertain significance ★ ⚠ same type
CTSS p.Asp74Asn Uncertain significance ★ ⚠ same type
CTSS p.Gly176Val Uncertain significance ★ ⚠ same type
CTSS p.His27Gln Uncertain significance ★ ⚠ same type
CTSS p.Ile193Thr Uncertain significance ★ ⚠ same type
CTSS p.Lys178Asn Uncertain significance ★ ⚠ same type
CTSS p.Lys212Gln Uncertain significance ★ ⚠ 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/ctss-p-asp120ala (accessed [today's date]).

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