Is ACP5 p.Ala25fs (c.71dup) pathogenic?

ACP5 p.Ala25fs (c.71dup) is classified Pathogenic in ACP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-03). Associated with Spondyloenchondrodysplasia with immune dysregulation.

What condition is associated with ACP5 p.Ala25fs (c.71dup)?

ACP5 p.Ala25fs (c.71dup) is associated with Spondyloenchondrodysplasia with immune dysregulation (ClinVar).

ACP5 p.Ala25fs

c.71dup · VCV4765104

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Spondyloenchondrodysplasia with immune dysregulation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -1.7

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ACP5
Protein: p.Ala25fs
Coding: c.71dup
MANE Select: NM_001611
Type: Duplication
Location: chr19:11577246 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.82 · 2 PDB

Full ACP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Spondyloenchondrodysplasia with immune dysregulation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACP5 p.Lys125Ter Pathogenic ★ same condition
ACP5 p.Tyr306Ter Uncertain significance ★ same condition
ACP5 p.Lys273fs Pathogenic same condition
ACP5 p.Arg176Ter Pathogenic ★★ same condition
ACP5 p.Gln184Ter Pathogenic/Likely pathogenic ★★ same condition
ACP5 p.Gly109Arg Pathogenic/Likely pathogenic ★★ same condition
ACP5 p.Met264Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ACP5 p.Ser258fs Pathogenic/Likely pathogenic ★★ 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/acp5-p-ala25fs (accessed [today's date]).

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