Is TMPRSS3 p.Tyr150= (c.450T>C) pathogenic?

TMPRSS3 p.Tyr150= (c.450T>C) is classified Uncertain significance in TMPRSS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Absent from gnomAD v4.1; Associated with autosomal recessive nonsyndromic hearing loss 8.

What condition is associated with TMPRSS3 p.Tyr150= (c.450T>C)?

TMPRSS3 p.Tyr150= (c.450T>C) is associated with autosomal recessive nonsyndromic hearing loss 8 (ClinVar).

How common is TMPRSS3 p.Tyr150= (c.450T>C) in the general population?

TMPRSS3 p.Tyr150= (c.450T>C) is absent from gnomAD v4.1 (gnomAD).

TMPRSS3 p.Tyr150=

c.450T>C · rs2052620435 · VCV896949

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal recessive nonsyndromic hearing loss 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.7	GERP -3.3
Overall
CADD	0.248	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TMPRSS3
Protein: p.Tyr150=
Coding: c.450T>C
MANE Select: NM_001256317
dbSNP: rs2052620435
Type: single nucleotide variant
Location: chr21:42385531 (GRCh38)
Gene constraint: LOEUF 1.106 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.09
Residue 150: the srcr domain

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 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
TMPRSS3 c.573-1G>A Likely pathogenic ★★ same condition
TMPRSS3 p.Ala138Glu Pathogenic/Likely pathogenic ★★ same condition
TMPRSS3 p.Ala306Thr Pathogenic/Likely pathogenic ★★ same condition
TMPRSS3 p.Ala306Val 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-tyr150 (accessed [today's date]).

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