Is ACP3 p.Arg332Trp (c.994C>T) pathogenic?

ACP3 p.Arg332Trp (c.994C>T) is classified Uncertain significance in ACP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: ambiguous (0.4219); Ultra-rare (popmax 0.0166%, mid).

How common is ACP3 p.Arg332Trp (c.994C>T) in the general population?

ACP3 p.Arg332Trp (c.994C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about ACP3 p.Arg332Trp (c.994C>T)?

AlphaMissense predicts ambiguous (score 0.4219) — an in-silico prediction, not a clinical call.

ACP3 p.Arg332Trp

c.994C>T · rs770158263 · VCV3138856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4219 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Computational evidence

Protein change
AlphaMissense	0.4219	ambiguous
REVEL	0.331	indeterminate
SaProt	LLR -15.14	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP 0.77, phastCons 0.85
Regional constraint	o/e 1.01	unconstrained · MANE · 39 kb · p 0.9 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.0166% Middle Eastern · 1/6,030 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00173% 28/1,613,906 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,030
African / African-American	0.00267%	37,442
European (non-Finnish)	0.00203%	49,168
South Asian	0.0011%	91,066

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: ACP3
Protein: p.Arg332Trp
Coding: c.994C>T
MANE Select: NM_001099
dbSNP: rs770158263
Type: single nucleotide variant
Location: chr3:132356711 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.51 · 17 PDB
Residue 332: a disulfide bond; a β-strand

Full ACP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP3 p.Arg332Gln Uncertain significance ★ ⚠ same residue
ACP3 p.Asp301Glu Benign ★★ same type
ACP3 p.Ala116Ser Uncertain significance ★ ⚠ same type
ACP3 p.Ala121Ser Uncertain significance ★ ⚠ same type
ACP3 p.Ala311Thr Uncertain significance ★ ⚠ same type
ACP3 p.Ala4Thr Uncertain significance ★ ⚠ same type
ACP3 p.Ala9Thr Uncertain significance ★ ⚠ same type
ACP3 p.Arg111Gln 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/acp3-p-arg332trp (accessed [today's date]).

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