Is TYRO3 p.Ser103Arg (c.309C>A) pathogenic?

TYRO3 p.Ser103Arg (c.309C>A) is classified Uncertain significance in TYRO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: ambiguous (0.3907); Very rare (popmax 0.00703%, eas).

How common is TYRO3 p.Ser103Arg (c.309C>A) in the general population?

TYRO3 p.Ser103Arg (c.309C>A) is very rare (popmax 0.00703%, eas) (gnomAD).

What do computational predictors say about TYRO3 p.Ser103Arg (c.309C>A)?

AlphaMissense predicts ambiguous (score 0.3907) — an in-silico prediction, not a clinical call.

TYRO3 p.Ser103Arg

c.309C>A · rs753643768 · VCV3185262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00703%, eas)

Computational evidence

Protein change
AlphaMissense	0.3907	ambiguous
REVEL	0.322	indeterminate
SaProt	LLR -5.17	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 19 kb · p 8.2e-20 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00703% East Asian · 3/42,662 alleles

Filtering AF 0.00186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00102%

Overall 0.00019% 3/1,579,854 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TYRO3
Protein: p.Ser103Arg
Coding: c.309C>A
MANE Select: NM_006293
dbSNP: rs753643768
Type: single nucleotide variant
Location: chr15:41561539 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 75.25 · 1 PDB
Residue 103: a disulfide bond; a β-strand; the ig-like c2-type 1 domain

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-ser103arg (accessed [today's date]).

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