Is ACP5 p.Phe167Ser (c.500T>C) pathogenic?

ACP5 p.Phe167Ser (c.500T>C) is classified Uncertain significance in ACP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-18). AlphaMissense: likely pathogenic (0.7805); Absent from gnomAD v4.1; Associated with Spondyloenchondrodysplasia with immune dysregulation.

What condition is associated with ACP5 p.Phe167Ser (c.500T>C)?

ACP5 p.Phe167Ser (c.500T>C) is associated with Spondyloenchondrodysplasia with immune dysregulation (ClinVar).

How common is ACP5 p.Phe167Ser (c.500T>C) in the general population?

ACP5 p.Phe167Ser (c.500T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACP5 p.Phe167Ser (c.500T>C)?

AlphaMissense predicts likely pathogenic (score 0.7805) — an in-silico prediction, not a clinical call.

ACP5 p.Phe167Ser

c.500T>C · rs764197394 · VCV1349238

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7805 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Spondyloenchondrodysplasia with immune dysregulation

Computational evidence

Protein change
AlphaMissense	0.7805	likely pathogenic
REVEL	0.502	indeterminate
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
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	26.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACP5
Protein: p.Phe167Ser
Coding: c.500T>C
MANE Select: NM_001611
dbSNP: rs764197394
Type: single nucleotide variant
Location: chr19:11576478 (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 167: a disulfide bond

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-phe167ser (accessed [today's date]).

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