Is TONSL p.Ser907fs (c.2721del) pathogenic?

TONSL p.Ser907fs (c.2721del) is classified Pathogenic in TONSL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-09). No gnomAD frequency available for this variant.

How common is TONSL p.Ser907fs (c.2721del) in the general population?

TONSL p.Ser907fs (c.2721del) is no gnomAD frequency available for this variant (gnomAD).

TONSL p.Ser907fs

c.2721del · rs1444877227 · VCV2002537

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -8.9	GERP -2.4

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ser907fs
Coding: c.2721del
MANE Select: NM_013432
dbSNP: rs1444877227
Type: Deletion
Location: chr8:144435712 (GRCh38)
Gene constraint: LOEUF 1.024 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.06 · 3 PDB
Residue 907: the 'disordered' region; a UniProt-annotated variant site (in semdsp; disease phenotype includes immunologic and hematologic abnormalities); a UniProt-annotated variant site (in semdsp); a UniProt-annotated variant site (in semdsp; disease phenotype includes primary aphakia and absent pupils)

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

Similar variants

TONSL p.Ser907Asn Uncertain significance ★ ⚠ same residue
TONSL p.Ser907= Likely benign ★ same residue
TONSL p.Ser1183fs Pathogenic ★★ same type
TONSL c.3006_3006+1del Likely pathogenic ★ same type
TONSL c.3387+1_3387+19del Likely pathogenic ★ same type
TONSL c.740_750+17del Likely pathogenic ★ same type
TONSL p.Ala371fs Pathogenic ★ same type
TONSL p.Asn182fs 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/tonsl-p-ser907fs (accessed [today's date]).

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