Is APEX2 p.Gly485Ala (c.1454G>C) pathogenic?

APEX2 p.Gly485Ala (c.1454G>C) is classified Uncertain significance in APEX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). AlphaMissense: ambiguous (0.5334); Absent from gnomAD v4.1.

How common is APEX2 p.Gly485Ala (c.1454G>C) in the general population?

APEX2 p.Gly485Ala (c.1454G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APEX2 p.Gly485Ala (c.1454G>C)?

AlphaMissense predicts ambiguous (score 0.5334) — an in-silico prediction, not a clinical call.

APEX2 p.Gly485Ala

c.1454G>C · rs2519568141 · VCV2536796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5334 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5334	ambiguous
REVEL	0.587	indeterminate
SaProt	LLR -14.88	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 7,009 bp · p 0.00024 · regional, not allelic
Overall
CADD	25.7	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

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: APEX2
Protein: p.Gly485Ala
Coding: c.1454G>C
MANE Select: NM_014481
dbSNP: rs2519568141
Type: single nucleotide variant
Location: chrX:55007332 (GRCh38)
Structure: AlphaFold pLDDT 78.87

Full APEX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APEX2 p.Ala309= Benign ★★ same type
APEX2 p.Ala83= Benign ★★ same type
APEX2 p.Arg141Cys Likely benign ★★ same type
APEX2 p.Ala126Ser Uncertain significance ★ ⚠ same type
APEX2 p.Ala160Val Uncertain significance ★ ⚠ same type
APEX2 p.Ala267Thr Uncertain significance ★ ⚠ same type
APEX2 p.Ala29Ser Uncertain significance ★ ⚠ same type
APEX2 p.Ala372Gly 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/apex2-p-gly485ala (accessed [today's date]).

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