Is ACP5 p.Leu201= (c.601C>T) pathogenic?

ACP5 p.Leu201= (c.601C>T) is classified Benign/Likely benign in ACP5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-23). Rare (popmax 0.29%, sas); Associated with Spondyloenchondrodysplasia with immune dysregulation.

What condition is associated with ACP5 p.Leu201= (c.601C>T)?

ACP5 p.Leu201= (c.601C>T) is associated with Spondyloenchondrodysplasia with immune dysregulation (ClinVar).

How common is ACP5 p.Leu201= (c.601C>T) in the general population?

ACP5 p.Leu201= (c.601C>T) is rare (popmax 0.29%, sas) (gnomAD).

ACP5 p.Leu201=

c.601C>T · rs568957938 · VCV533476

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.29%, sas)

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 5.1	GERP -1.8, phastCons 1
Overall
CADD	4.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.29% South Asian · 264/91,010 alleles

Filtering AF 0.261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.25%

Overall 0.0352% 567/1,610,788 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.29%	345
Middle Eastern	0.288%	348
Remaining individualsnot grpmax-eligible	0.0562%	1,780
European (non-Finnish)	0.0204%	4,909
Admixed American	0.00667%	14,989
Finnishnot grpmax-eligible	0.00634%	15,783
African / African-American	0.00267%	37,490
East Asian	0.00223%	44,782

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.Leu201=
Coding: c.601C>T
MANE Select: NM_001611
dbSNP: rs568957938
Type: single nucleotide variant
Location: chr19:11576377 (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 201: a disulfide bond; a UniProt-annotated variant site (in spencdi); a β-strand

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.Leu201Pro 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
ACP5 p.Tyr74Ter 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-leu201 (accessed [today's date]).

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