Is ACP5 p.Ala193= (c.579G>A) pathogenic?

ACP5 p.Ala193= (c.579G>A) is classified Likely benign in ACP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-23). Ultra-rare (popmax 0.0117%, amr); Associated with Spondyloenchondrodysplasia with immune dysregulation.

What condition is associated with ACP5 p.Ala193= (c.579G>A)?

ACP5 p.Ala193= (c.579G>A) is associated with Spondyloenchondrodysplasia with immune dysregulation (ClinVar).

How common is ACP5 p.Ala193= (c.579G>A) in the general population?

ACP5 p.Ala193= (c.579G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

ACP5 p.Ala193=

c.579G>A · rs752926629 · VCV1537818

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

Spondyloenchondrodysplasia with immune dysregulation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.4	GERP -3.5
Overall
CADD	0.829	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,980 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000992% 16/1,612,280 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,569
East Asian	0.00223%	44,840
Remaining individualsnot grpmax-eligible	0.0016%	62,392
African / African-American	0.00134%	74,878
South Asian	0.0011%	91,062
European (non-Finnish)	0.000424%	235,801

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.Ala193=
Coding: c.579G>A
MANE Select: NM_001611
dbSNP: rs752926629
Type: single nucleotide variant
Location: chr19:11576399 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.82 · 2 PDB
Residue 193: a disulfide bond; an α-helix

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.Ala193Glu Uncertain significance ★ ⚠ same residue
ACP5 p.Ala193Val Uncertain significance ★ ⚠ same residue
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.Tyr123Ter Pathogenic ★★ same condition
ACP5 p.Tyr246Ter 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-ala193 (accessed [today's date]).

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