Is CTSA p.Gln369Pro (c.1106A>C) pathogenic?

CTSA p.Gln369Pro (c.1106A>C) is classified Uncertain significance in CTSA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: ambiguous (0.3503); Rare (popmax 0.267%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTSA p.Gln369Pro (c.1106A>C)?

CTSA p.Gln369Pro (c.1106A>C) is associated with Inborn genetic diseases (ClinVar).

How common is CTSA p.Gln369Pro (c.1106A>C) in the general population?

CTSA p.Gln369Pro (c.1106A>C) is rare (popmax 0.267%, nfe) (gnomAD).

What do computational predictors say about CTSA p.Gln369Pro (c.1106A>C)?

AlphaMissense predicts ambiguous (score 0.3503) — an in-silico prediction, not a clinical call.

CTSA p.Gln369Pro

c.1106A>C · rs1357381119 · VCV2281876

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3503 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.267%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3503	ambiguous
REVEL	0.494	indeterminate
SaProt	LLR -12.10	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 4,432 bp · p 0.0086 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.267% European (non-Finnish) · 3,125/1,168,854 alleles

Filtering AF 0.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.256%

Overall 0.216% 3,459/1,601,462 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.267%	374
Remaining individualsnot grpmax-eligible	0.209%	477
Ashkenazi Jewishnot grpmax-eligible	0.108%	922
South Asian	0.087%	1,150
African / African-American	0.0802%	1,247
Middle Eastern	0.0663%	1,509
East Asian	0.0381%	2,627
Admixed American	0.01%	9,994
Finnishnot grpmax-eligible	0.0094%	10,638

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: CTSA
Protein: p.Gln369Pro
Coding: c.1106A>C
MANE Select: NM_000308
dbSNP: rs1357381119
Type: single nucleotide variant
Location: chr20:45896982 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB
Residue 369: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTSA p.Gln369Ter Pathogenic/Likely pathogenic ★★ same residue
CTSA p.Gln369fs Pathogenic ★★ same residue
CTSA c.-17G>A Uncertain significance ★★ same condition
CTSA c.-41C>T Uncertain significance ★★ same condition
CTSA c.-6G>A Uncertain significance ★★ same condition
CTSA p.Ala150Thr Uncertain significance ★★ ⚠ same condition
CTSA p.Arg372Cys Uncertain significance ★★ ⚠ same condition
CTSA p.Gly454Val Uncertain significance ★★ ⚠ same condition

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/ctsa-p-gln369pro (accessed [today's date]).

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