Is ACP2 p.Glu174Asp (c.522G>C) pathogenic?

ACP2 p.Glu174Asp (c.522G>C) is classified Uncertain significance in ACP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: likely benign (0.2066); Absent from gnomAD v4.1.

How common is ACP2 p.Glu174Asp (c.522G>C) in the general population?

ACP2 p.Glu174Asp (c.522G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACP2 p.Glu174Asp (c.522G>C)?

AlphaMissense predicts likely benign (score 0.2066) — an in-silico prediction, not a clinical call.

ACP2 p.Glu174Asp

c.522G>C · rs1954034473 · VCV2247420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2066 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2066	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -8.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.51	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 8,670 bp · p 0.0021 · regional, not allelic
Overall
CADD	18.97	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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: ACP2
Protein: p.Glu174Asp
Coding: c.522G>C
MANE Select: NM_001610
dbSNP: rs1954034473
Type: single nucleotide variant
Location: chr11:47245501 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.09
Residue 174: a disulfide bond

Full ACP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP2 c.856-4G>A Benign ★★ same type
ACP2 p.Arg10Trp Likely benign ★★ same type
ACP2 p.Phe393Leu Benign/Likely benign ★★ same type
ACP2 p.Val416= Benign ★★ same type
ACP2 p.Ala11Glu Uncertain significance ★ ⚠ same type
ACP2 p.Ala272Val Uncertain significance ★ ⚠ same type
ACP2 p.Ala336Thr Uncertain significance ★ ⚠ same type
ACP2 p.Ala336Val Uncertain significance ★ ⚠ same type

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/acp2-p-glu174asp (accessed [today's date]).

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