Is CTSA p.Trp65Ter (c.195G>A) pathogenic?

CTSA p.Trp65Ter (c.195G>A) is classified Pathogenic in CTSA (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-07). Very rare (popmax 0.0011%, sas).

How common is CTSA p.Trp65Ter (c.195G>A) in the general population?

CTSA p.Trp65Ter (c.195G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

CTSA p.Trp65Ter

c.195G>A · rs1568761792 · VCV620166

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 15
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 10	GERP 1.8, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 6.84e-05% 1/1,461,686 alleles · very rare

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.Trp65Ter
Coding: c.195G>A
MANE Select: NM_000308
dbSNP: rs1568761792
Type: single nucleotide variant
Location: chr20:45891916 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB
Residue 65: a UniProt-annotated variant site (in gsl); a β-strand

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

Similar variants

CTSA p.Trp65Arg Pathogenic same residue
CTSA c.1-2A>G Pathogenic/Likely pathogenic ★★ same type
CTSA c.358-2A>G Likely pathogenic ★★ same type
CTSA c.601-2A>G Pathogenic/Likely pathogenic ★★ same type
CTSA c.692+3A>G Pathogenic ★★ same type
CTSA c.948+1G>A Likely pathogenic ★★ same type
CTSA p.Arg375Ter Pathogenic/Likely pathogenic ★★ same type
CTSA p.Cys256Ter 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/ctsa-p-trp65ter (accessed [today's date]).

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