Is FBXO7 p.Asn135Tyr (c.403A>T) pathogenic?

FBXO7 p.Asn135Tyr (c.403A>T) is classified Uncertain significance in FBXO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-17). AlphaMissense: likely benign (0.104); Absent from gnomAD v4.1.

How common is FBXO7 p.Asn135Tyr (c.403A>T) in the general population?

FBXO7 p.Asn135Tyr (c.403A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FBXO7 p.Asn135Tyr (c.403A>T)?

AlphaMissense predicts likely benign (score 0.104) — an in-silico prediction, not a clinical call.

FBXO7 p.Asn135Tyr

c.403A>T · rs2544655320 · VCV2573734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.104 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.104	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -8.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.39	donor gain · deltas
Constraint at this position
Conservation	phyloP 2.8	GERP -0.84, phastCons 0.94
Regional constraint	o/e 1.03	unconstrained · MANE · 24 kb · p 0.42 · regional, not allelic
Overall
CADD	22.4	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: FBXO7
Protein: p.Asn135Tyr
Coding: c.403A>T
MANE Select: NM_012179
dbSNP: rs2544655320
Type: single nucleotide variant
Location: chr22:32479261 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.13 · 2 PDB
Residue 135: the 'disordered' region; the 'important for interaction with cdk6' region

Full FBXO7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FBXO7 p.Arg321Ter Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Arg345Ter Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Arg381Ter Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Arg45Ter Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Arg498Ter Pathogenic ★★ same type
FBXO7 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Thr22Met Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Ala84Val 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/fbxo7-p-asn135tyr (accessed [today's date]).

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