Is ACP4 p.Arg161Gln (c.482G>A) pathogenic?

ACP4 p.Arg161Gln (c.482G>A) is classified Uncertain significance in ACP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely benign (0.1008); Ultra-rare (popmax 0.0155%, amr).

How common is ACP4 p.Arg161Gln (c.482G>A) in the general population?

ACP4 p.Arg161Gln (c.482G>A) is ultra-rare (popmax 0.0155%, amr) (gnomAD).

What do computational predictors say about ACP4 p.Arg161Gln (c.482G>A)?

AlphaMissense predicts likely benign (score 0.1008) — an in-silico prediction, not a clinical call.

ACP4 p.Arg161Gln

c.482G>A · VCV3825000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1008 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0155%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1008	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -10.79	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.9, phastCons 0.64
Regional constraint	o/e 1.03	unconstrained · MANE · 4,740 bp · p 0.54 · regional, not allelic
Overall
CADD	22.4	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 0.0155% Admixed American · 9/57,952 alleles

Filtering AF 0.00808% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00596%

Overall 0.00125% 20/1,601,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0155%	6,439
Remaining individualsnot grpmax-eligible	0.00485%	20,623
East Asian	0.00225%	44,498
African / African-American	0.00134%	74,768
South Asian	0.00111%	89,768
European (non-Finnish)	0.000425%	235,095

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: ACP4
Protein: p.Arg161Gln
Coding: c.482G>A
MANE Select: NM_033068
Type: single nucleotide variant
Location: chr19:50792104 (GRCh38)
Gene constraint: LOEUF 1.413 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.30
Residue 161: a disulfide bond

Full ACP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP4 p.Arg111Cys Pathogenic/Likely pathogenic ★★ same type
ACP4 c.550-4C>T Benign ★★ same type
ACP4 c.550-9C>T Benign ★★ same type
ACP4 p.Gly328Ala Benign ★★ same type
ACP4 p.Pro125= Benign ★★ same type
ACP4 c.645+1G>A Likely pathogenic ★ same type
ACP4 p.Leu85Pro Pathogenic ★ same type
ACP4 p.Met282Thr Pathogenic ★ ⚠ 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/acp4-p-arg161gln (accessed [today's date]).

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