Is TONSL p.Gln88Ter (c.262C>T) pathogenic?

TONSL p.Gln88Ter (c.262C>T) is classified Likely pathogenic in TONSL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). No allele count reported in gnomAD v4.1 (AN 1,545,130); Associated with Susceptibility to severe COVID-19.

What condition is associated with TONSL p.Gln88Ter (c.262C>T)?

TONSL p.Gln88Ter (c.262C>T) is associated with Susceptibility to severe COVID-19 (ClinVar).

How common is TONSL p.Gln88Ter (c.262C>T) in the general population?

TONSL p.Gln88Ter (c.262C>T) is no allele count reported in gnomAD v4.1 (AN 1,545,130) (gnomAD).

TONSL p.Gln88Ter

c.262C>T · VCV3256942

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,545,130)

Conditions

Susceptibility to severe COVID-19

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 26
Splicing
SpliceAI	Δ0.90	donor gain · deltas
Pangolin	Δ0.71	gain · loss 0.39 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.7	GERP -3.3, phastCons 1
Overall
CADD	41.0	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

No allele count reported in gnomAD v4.1 (AN 1,545,130). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TONSL
Protein: p.Gln88Ter
Coding: c.262C>T
MANE Select: NM_013432
Type: single nucleotide variant
Location: chr8:144443884 (GRCh38)
Gene constraint: LOEUF 1.024 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.06 · 3 PDB

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

Disease context

Susceptibility to severe COVID-19

Similar variants

TONSL p.Gln88His Uncertain significance ★ ⚠ same residue
TONSL p.Gln88Pro Uncertain significance ★ same residue
TONSL p.Arg875Ter Pathogenic/Likely pathogenic ★★ same condition
TONSL p.Gln177Ter Pathogenic/Likely pathogenic ★★ same condition
TONSL p.Arg382His Uncertain significance ★★ ⚠ same condition
TONSL p.Glu199Lys Uncertain significance ★★ same condition
TONSL c.3007-2A>C Likely pathogenic ★ same condition
TONSL c.866-1G>C 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/tonsl-p-gln88ter (accessed [today's date]).

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