Is ACP5 p.Ser267fs (c.799del) pathogenic?

ACP5 p.Ser267fs (c.799del) is classified Pathogenic in ACP5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-11). Very rare (popmax 0.00203%, nfe); Associated with Spondyloenchondrodysplasia with immune dysregulation.

What condition is associated with ACP5 p.Ser267fs (c.799del)?

ACP5 p.Ser267fs (c.799del) is associated with Spondyloenchondrodysplasia with immune dysregulation (ClinVar).

How common is ACP5 p.Ser267fs (c.799del) in the general population?

ACP5 p.Ser267fs (c.799del) is very rare (popmax 0.00203%, nfe) (gnomAD).

ACP5 p.Ser267fs

c.799del · rs1294990891 · VCV1455117

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

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	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,180,036 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00155% 25/1,613,972 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,168
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: ACP5
Protein: p.Ser267fs
Coding: c.799del
MANE Select: NM_001611
dbSNP: rs1294990891
Type: Deletion
Location: chr19:11575189 (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.Ser258fs Pathogenic/Likely pathogenic ★★ same condition
ACP5 p.Tyr278del Uncertain significance ★★ same condition
ACP5 p.Arg176fs Pathogenic ★ same condition
ACP5 p.Arg46fs Pathogenic ★ same condition
ACP5 p.Cys219fs Pathogenic ★ same condition
ACP5 p.Gln87fs Pathogenic ★ same condition
ACP5 p.Ile121fs Pathogenic ★ same condition
ACP5 p.Leu15fs 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-ser267fs (accessed [today's date]).

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