Is TMPRSS3 p.Ala33fs (c.97del) pathogenic?

TMPRSS3 p.Ala33fs (c.97del) is classified Pathogenic in TMPRSS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). No gnomAD frequency available for this variant.

How common is TMPRSS3 p.Ala33fs (c.97del) in the general population?

TMPRSS3 p.Ala33fs (c.97del) is no gnomAD frequency available for this variant (gnomAD).

TMPRSS3 p.Ala33fs

c.97del · rs2146452576 · VCV1454077

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 3 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.2	GERP 2, phastCons 1

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: TMPRSS3
Protein: p.Ala33fs
Coding: c.97del
MANE Select: NM_001256317
dbSNP: rs2146452576
Type: Deletion
Location: chr21:42390035 (GRCh38)
Gene constraint: LOEUF 1.106 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.09

Full TMPRSS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TMPRSS3 p.Asp334fs Pathogenic/Likely pathogenic ★★ same type
TMPRSS3 p.Gln144fs Pathogenic ★★ same type
TMPRSS3 p.His70fs Pathogenic/Likely pathogenic ★★ same type
TMPRSS3 p.Ser215fs Pathogenic/Likely pathogenic ★★ same type
TMPRSS3 p.Val337fs Pathogenic/Likely pathogenic ★★ same type
TMPRSS3 p.Ala345fs Pathogenic ★ same type
TMPRSS3 p.Asp23_Leu24insTer Pathogenic ★ same type
TMPRSS3 p.Leu250fs 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/tmprss3-p-ala33fs (accessed [today's date]).

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