Is TMPRSS3 p.Pro50fs (c.147dup) pathogenic?

TMPRSS3 p.Pro50fs (c.147dup) is classified Pathogenic in TMPRSS3 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-31). No gnomAD frequency available for this variant; Associated with autosomal recessive nonsyndromic hearing loss 8.

What condition is associated with TMPRSS3 p.Pro50fs (c.147dup)?

TMPRSS3 p.Pro50fs (c.147dup) is associated with autosomal recessive nonsyndromic hearing loss 8 (ClinVar).

How common is TMPRSS3 p.Pro50fs (c.147dup) in the general population?

TMPRSS3 p.Pro50fs (c.147dup) is no gnomAD frequency available for this variant (gnomAD).

TMPRSS3 p.Pro50fs

c.147dup · rs2146452391 · VCV1185654

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal recessive nonsyndromic hearing loss 8

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 9.6	GERP 0.99, 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.Pro50fs
Coding: c.147dup
MANE Select: NM_001256317
dbSNP: rs2146452391
Type: Duplication
Location: chr21:42389984 (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

Disease context

autosomal recessive nonsyndromic hearing loss 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TMPRSS3 p.Cys194fs Pathogenic/Likely pathogenic ★★ same condition
TMPRSS3 c.617-3_617-2dup Benign ★★ same condition
TMPRSS3 p.Pro403fs Likely pathogenic ★ same condition
TMPRSS3 p.Ser14fs Pathogenic ★ same condition
TMPRSS3 c.1049-4G>A Likely pathogenic ★★ same condition
TMPRSS3 c.206-2A>G Likely pathogenic ★★ same condition
TMPRSS3 c.323-6G>A Pathogenic/Likely pathogenic ★★ same condition
TMPRSS3 c.446+1G>T Likely pathogenic ★★ 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/tmprss3-p-pro50fs (accessed [today's date]).

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