Is LYN p.Val45Phe (c.133G>T) pathogenic?

LYN p.Val45Phe (c.133G>T) is classified Uncertain significance in LYN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0856); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LYN p.Val45Phe (c.133G>T)?

LYN p.Val45Phe (c.133G>T) is associated with Inborn genetic diseases (ClinVar).

How common is LYN p.Val45Phe (c.133G>T) in the general population?

LYN p.Val45Phe (c.133G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LYN p.Val45Phe (c.133G>T)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

LYN p.Val45Phe

c.133G>T · VCV4624045

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -8.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	loss · gain 0.04 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 10 kb · p 0.0091 · regional, not allelic
Overall
CADD	21.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LYN
Protein: p.Val45Phe
Coding: c.133G>T
MANE Select: NM_002350
Type: single nucleotide variant
Location: chr8:55946448 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.44 · 6 PDB
Residue 45: the 'disordered' region

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.Val45Ile Uncertain significance ★★ ⚠ same residue
LYN p.Ala150Thr Uncertain significance ★★ ⚠ same condition
LYN p.Ala70Thr Uncertain significance ★★ ⚠ same condition
LYN p.Arg360Trp 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.Ala307Thr 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-val45phe (accessed [today's date]).

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