Is TYRO3 p.Ala815Val (c.2444C>T) pathogenic?

TYRO3 p.Ala815Val (c.2444C>T) is classified Benign in TYRO3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-08). AlphaMissense: likely benign (0.0725); Low-frequency (popmax 1.32%, afr).

How common is TYRO3 p.Ala815Val (c.2444C>T) in the general population?

TYRO3 p.Ala815Val (c.2444C>T) is low-frequency (popmax 1.32%, afr) (gnomAD).

What do computational predictors say about TYRO3 p.Ala815Val (c.2444C>T)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

TYRO3 p.Ala815Val

c.2444C>T · rs1042057 · VCV730048

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.32%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -7.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -1.7, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 19 kb · p 8.2e-20 · regional, not allelic
Overall
CADD	1.576	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 1.32% African / African-American · 993/75,010 alleles

Filtering AF 1.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.23%

Overall 0.0672% 1,085/1,614,018 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.32%	76
Remaining individualsnot grpmax-eligible	0.0624%	1,603
Admixed American	0.0566%	1,765
Middle Eastern	0.0166%	6,024
East Asian	0.00446%	22,439
South Asian	0.00439%	22,765
European (non-Finnish)	0.00102%	98,334

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.Ala815Val
Coding: c.2444C>T
MANE Select: NM_006293
dbSNP: rs1042057
Type: single nucleotide variant
Location: chr15:41578047 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 75.25 · 1 PDB
Residue 815: the 'disordered' region; a UniProt-annotated variant site (in)

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

Similar variants

TYRO3 p.Ala815= Benign ★★ same residue
TYRO3 p.Ser543Phe Uncertain significance ★★ ⚠ 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
TYRO3 p.Ala149Val 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-ala815val (accessed [today's date]).

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