Is AOX1 p.Ser987Phe (c.2960C>T) pathogenic?

AOX1 p.Ser987Phe (c.2960C>T) is classified Uncertain significance in AOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely benign (0.0979); Absent from gnomAD v4.1.

How common is AOX1 p.Ser987Phe (c.2960C>T) in the general population?

AOX1 p.Ser987Phe (c.2960C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AOX1 p.Ser987Phe (c.2960C>T)?

AlphaMissense predicts likely benign (score 0.0979) — an in-silico prediction, not a clinical call.

AOX1 p.Ser987Phe

c.2960C>T · VCV3876444

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0979	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -9.80	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 0.33	GERP 4.2
Regional constraint	o/e 1.00	unconstrained · MANE · 85 kb · p 0.85 · regional, not allelic
Overall
CADD	12.21	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: AOX1
Protein: p.Ser987Phe
Coding: c.2960C>T
MANE Select: NM_001159
Type: single nucleotide variant
Location: chr2:200651086 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.13 · 8 PDB
Residue 987: an α-helix

Full AOX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AOX1 p.Ala1083Gly Benign ★★ same type
AOX1 p.Arg130= Benign ★★ same type
AOX1 p.Gln314Arg Benign ★★ same type
AOX1 p.Gln737= Benign ★★ same type
AOX1 p.Ile598Asn Benign ★★ ⚠ same type
AOX1 p.Leu553= Benign ★★ same type
AOX1 p.Pro1245= Benign ★★ same type
AOX1 p.Pro702= Likely benign ★★ 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/aox1-p-ser987phe (accessed [today's date]).

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