Is ACKR1 p.Gln161Arg (c.482A>G) pathogenic?

ACKR1 p.Gln161Arg (c.482A>G) is classified Uncertain significance in ACKR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). AlphaMissense: likely benign (0.0716); Ultra-rare (popmax 0.0165%, mid).

How common is ACKR1 p.Gln161Arg (c.482A>G) in the general population?

ACKR1 p.Gln161Arg (c.482A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ACKR1 p.Gln161Arg (c.482A>G)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

ACKR1 p.Gln161Arg

c.482A>G · rs754054567 · VCV2404106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -5.36	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 0.045	GERP -0.36
Regional constraint	o/e 1.11	unconstrained · MANE · 1,487 bp · p 0.031 · regional, not allelic
Overall
CADD	13.87	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

Grpmax group 0.0165% Middle Eastern · 1/6,070 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00235% 38/1,613,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,070
European (non-Finnish)	0.00288%	34,705
Remaining individualsnot grpmax-eligible	0.0016%	62,480
Finnishnot grpmax-eligible	0.00156%	63,954
African / African-American	0.00133%	74,944

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: ACKR1
Protein: p.Gln161Arg
Coding: c.482A>G
MANE Select: NM_002036
dbSNP: rs754054567
Type: single nucleotide variant
Location: chr1:159205921 (GRCh38)
Gene constraint: LOEUF 1.841 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 78.25 · 6 PDB
Residue 161: a disulfide bond

Full ACKR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACKR1 p.Arg89Cys Likely benign ★★ same type
ACKR1 p.Gly238= Benign ★★ same type
ACKR1 p.Gly42Asp Benign ★★ same type
ACKR1 p.Ala144Pro Uncertain significance ★ ⚠ same type
ACKR1 p.Ala49Val Uncertain significance ★ ⚠ same type
ACKR1 p.Asn244Ser Uncertain significance ★ ⚠ same type
ACKR1 p.Asp283Gly Uncertain significance ★ ⚠ same type
ACKR1 p.Cys51Trp 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/ackr1-p-gln161arg (accessed [today's date]).

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