Is TYRO3 p.Val119Leu (c.355G>T) pathogenic?

TYRO3 p.Val119Leu (c.355G>T) is classified Uncertain significance in TYRO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-04). AlphaMissense: likely benign (0.2071); Absent from gnomAD v4.1.

How common is TYRO3 p.Val119Leu (c.355G>T) in the general population?

TYRO3 p.Val119Leu (c.355G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TYRO3 p.Val119Leu (c.355G>T)?

AlphaMissense predicts likely benign (score 0.2071) — an in-silico prediction, not a clinical call.

TYRO3 p.Val119Leu

c.355G>T · VCV4600999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2071 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,595,310)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2071	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -9.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.34, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 19 kb · p 8.2e-20 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,595,310). 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.Val119Leu
Coding: c.355G>T
MANE Select: NM_006293
Type: single nucleotide variant
Location: chr15:41561585 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 75.25 · 1 PDB
Residue 119: the ig-like c2-type 1 domain; a β-strand

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

Similar variants

TYRO3 p.Ser543Phe Uncertain significance ★★ ⚠ same type
TYRO3 p.Ala815= Benign ★★ same type
TYRO3 p.Ala815Val Benign ★★ ⚠ same type
TYRO3 p.Gly675Arg Benign ★★ same type
TYRO3 p.Pro183= Benign ★★ same type
TYRO3 p.Thr458= Benign ★★ same type
TYRO3 p.Val669Leu Benign ★★ same type
TYRO3 p.Ala149Ser Uncertain significance ★ ⚠ 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/tyro3-p-val119leu (accessed [today's date]).

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