Is ACP5 p.Leu201Pro (c.602T>C) pathogenic?

ACP5 p.Leu201Pro (c.602T>C) is classified Uncertain significance in ACP5 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-03-12). AlphaMissense: likely pathogenic (0.98); Very rare (popmax 0.00017%, nfe); Associated with Spondyloenchondrodysplasia with immune dysregulation.

What condition is associated with ACP5 p.Leu201Pro (c.602T>C)?

ACP5 p.Leu201Pro (c.602T>C) is associated with Spondyloenchondrodysplasia with immune dysregulation (ClinVar).

How common is ACP5 p.Leu201Pro (c.602T>C) in the general population?

ACP5 p.Leu201Pro (c.602T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ACP5 p.Leu201Pro (c.602T>C)?

AlphaMissense predicts likely pathogenic (score 0.98) — an in-silico prediction, not a clinical call.

ACP5 p.Leu201Pro

c.602T>C · rs387906672 · VCV29835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.98 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Spondyloenchondrodysplasia with immune dysregulation

Computational evidence

Protein change
AlphaMissense	0.98	likely pathogenic · top 8% in ACP5
REVEL	0.865	moderately pathogenic-leaning
SaProt	LLR -17.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,304 bp · p 0.00091 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,018 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,458,398 alleles · very rare

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.Leu201Pro
Coding: c.602T>C
MANE Select: NM_001611
dbSNP: rs387906672
Type: single nucleotide variant
Location: chr19:11576376 (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.Leu201= Benign/Likely benign ★★ 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-leu201pro (accessed [today's date]).

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