Is LYN p.Arg360Trp (c.1078C>T) pathogenic?

LYN p.Arg360Trp (c.1078C>T) is classified Uncertain significance in LYN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-24). AlphaMissense: ambiguous (0.4881); Very rare (popmax 0.00449%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LYN p.Arg360Trp (c.1078C>T)?

LYN p.Arg360Trp (c.1078C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LYN p.Arg360Trp (c.1078C>T) in the general population?

LYN p.Arg360Trp (c.1078C>T) is very rare (popmax 0.00449%, nfe) (gnomAD).

What do computational predictors say about LYN p.Arg360Trp (c.1078C>T)?

AlphaMissense predicts ambiguous (score 0.4881) — an in-silico prediction, not a clinical call.

LYN p.Arg360Trp

c.1078C>T · rs144335088 · VCV1345363

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4881 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4881	ambiguous
REVEL	0.192	benign-leaning
SaProt	LLR -13.75	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -2.7, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 58 kb · p 1.8e-23 · regional, not allelic
Overall
CADD	25.5	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 0.00449% European (non-Finnish) · 53/1,179,562 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00359% 58/1,613,420 alleles · very rare exomes 54/1,461,320 · genomes 4/152,100 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00449%	22,256
Remaining individualsnot grpmax-eligible	0.0032%	31,232
Admixed American	0.00167%	59,982
African / African-American	0.00134%	74,886
South Asian	0.0011%	91,064

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: LYN
Protein: p.Arg360Trp
Coding: c.1078C>T
MANE Select: NM_002350
dbSNP: rs144335088
Type: single nucleotide variant
Location: chr8:55998373 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.44 · 6 PDB
Residue 360: the protein kinase domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LYN p.Arg360Leu Uncertain significance ★ ⚠ same residue
LYN p.Arg360Gln Uncertain significance ★ ⚠ same residue
LYN p.Ala150Thr Uncertain significance ★★ ⚠ same condition
LYN p.Ala70Thr Uncertain significance ★★ ⚠ same condition
LYN p.Glu47Asp Uncertain significance ★★ ⚠ same condition
LYN p.Ser333Asn Uncertain significance ★★ same condition
LYN p.Thr30Ala Uncertain significance ★★ ⚠ same condition
LYN p.Val45Ile Uncertain significance ★★ ⚠ 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/lyn-p-arg360trp (accessed [today's date]).

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