Is TYR p.Pro129fs (c.386del) pathogenic?

TYR p.Pro129fs (c.386del) is classified Likely pathogenic in TYR (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-18). Associated with TYR-related disorder.

What condition is associated with TYR p.Pro129fs (c.386del)?

TYR p.Pro129fs (c.386del) is associated with TYR-related disorder (ClinVar).

TYR p.Pro129fs

c.386del · VCV4913502

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

TYR-related disorder

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 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP -3.8, phastCons 0.002

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

Variant & gene context

Gene: TYR
Protein: p.Pro129fs
Coding: c.386del
MANE Select: NM_000372
Type: Deletion
Location: chr11:89178336 (GRCh38)
Gene constraint: LOEUF 1.346 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79 · 1 PDB

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

Disease context

TYR-related disorder

Similar variants

TYR p.Glu413fs Pathogenic/Likely pathogenic ★★ same condition
TYR p.Trp475fs Likely pathogenic ★★ same condition
TYR p.Gly227del Conflicting classifications of pathogenicity ★ same condition
TYR p.Ser315_Ala316del Likely pathogenic same condition
TYR c.1037-2A>G Pathogenic/Likely pathogenic ★★ same condition
TYR c.1366+1G>T Pathogenic/Likely pathogenic ★★ same condition
TYR p.Ala206Thr Pathogenic/Likely pathogenic ★★ same condition
TYR p.Arg212Lys Pathogenic/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/tyr-p-pro129fs (accessed [today's date]).

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