Is TYRO3 p.Ala223fs (c.666_667insCACTGCCTGC…[29 bp]) pathogenic?

TYRO3 p.Ala223fs (c.666667insCACTGCCTGC…[29 bp]) is classified Uncertain significance in TYRO3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-01-01). Absent from gnomAD; Associated with 46,XX disorder of sex development.

What condition is associated with TYRO3 p.Ala223fs (c.666_667insCACTGCCTGC…[29 bp])?

TYRO3 p.Ala223fs (c.666_667insCACTGCCTGC…[29 bp]) is associated with 46,XX disorder of sex development (ClinVar).

How common is TYRO3 p.Ala223fs (c.666_667insCACTGCCTGC…[29 bp]) in the general population?

TYRO3 p.Ala223fs (c.666_667insCACTGCCTGC…[29 bp]) is absent from gnomAD (gnomAD).

TYRO3 p.Ala223fs

c.666_667insCACTGCCTGC…[29 bp] · rs2550239426 · VCV2429362

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

46,XX disorder of sex development

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 5 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8	GERP 1.5, 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: TYRO3
Protein: p.Ala223fs
Coding: c.666_667insCACTGCCTGCAGCCCCCTTCAACATCACC
MANE Select: NM_006293
dbSNP: rs2550239426
Type: Insertion
Location: chr15:41564269 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 75.25 · 1 PDB

Full TYRO3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

46,XX disorder of sex development — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/tyro3-p-ala223fs (accessed [today's date]).

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