Is APEX2 p.Val384Ala (c.1151T>C) pathogenic?

APEX2 p.Val384Ala (c.1151T>C) is classified Likely benign in APEX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.0529); Ultra-rare (popmax 0.0473%, eas).

How common is APEX2 p.Val384Ala (c.1151T>C) in the general population?

APEX2 p.Val384Ala (c.1151T>C) is ultra-rare (popmax 0.0473%, eas) (gnomAD).

What do computational predictors say about APEX2 p.Val384Ala (c.1151T>C)?

AlphaMissense predicts likely benign (score 0.0529) — an in-silico prediction, not a clinical call.

APEX2 p.Val384Ala

c.1151T>C · VCV4123156

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0529 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0473%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0529	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -5.61	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 -0.58	GERP -2.8
Regional constraint	o/e 0.82	unconstrained · MANE · 7,009 bp · p 0.00024 · regional, not allelic
Overall
CADD	0.052	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 0.0473% East Asian · 16/33,811 alleles

Filtering AF 0.0297% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0241%

Overall 0.00182% 20/1,098,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0473%	2,113
Remaining individualsnot grpmax-eligible	0.0021%	47,641
European (non-Finnish)	0.000335%	298,476

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: APEX2
Protein: p.Val384Ala
Coding: c.1151T>C
MANE Select: NM_014481
Type: single nucleotide variant
Location: chrX:55007029 (GRCh38)
Structure: AlphaFold pLDDT 78.87
Residue 384: the 'disordered' region

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-val384ala (accessed [today's date]).

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