Is ACP5 p.Asp92= (c.276C>T) pathogenic?

ACP5 p.Asp92= (c.276C>T) is classified Benign in ACP5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.69%, afr); Associated with Spondyloenchondrodysplasia with immune dysregulation.

What condition is associated with ACP5 p.Asp92= (c.276C>T)?

ACP5 p.Asp92= (c.276C>T) is associated with Spondyloenchondrodysplasia with immune dysregulation (ClinVar).

How common is ACP5 p.Asp92= (c.276C>T) in the general population?

ACP5 p.Asp92= (c.276C>T) is low-frequency (popmax 1.69%, afr) (gnomAD).

ACP5 p.Asp92=

c.276C>T · rs34375794 · VCV464888

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.69%, afr)

Conditions

Spondyloenchondrodysplasia with immune dysregulation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.2	GERP -2.9
Overall
CADD	3.793	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.69% African / African-American · 1,265/75,006 alleles

Filtering AF 1.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.58%

Overall 0.109% 1,761/1,614,058 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.69%	59
Middle Eastern	0.297%	337
Admixed American	0.255%	392
Remaining individualsnot grpmax-eligible	0.163%	613
European (non-Finnish)	0.0182%	5,488
South Asian	0.00769%	13,011
East Asian	0.00223%	44,858

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.Asp92=
Coding: c.276C>T
MANE Select: NM_001611
dbSNP: rs34375794
Type: single nucleotide variant
Location: chr19:11576829 (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.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
ACP5 p.Ala19Val Uncertain significance ★★ ⚠ 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-asp92 (accessed [today's date]).

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