Is ACKR2 p.Trp169Ser (c.506G>C) pathogenic?

ACKR2 p.Trp169Ser (c.506G>C) is classified Uncertain significance in ACKR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely pathogenic (0.6566); Absent from gnomAD v4.1.

How common is ACKR2 p.Trp169Ser (c.506G>C) in the general population?

ACKR2 p.Trp169Ser (c.506G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACKR2 p.Trp169Ser (c.506G>C)?

AlphaMissense predicts likely pathogenic (score 0.6566) — an in-silico prediction, not a clinical call.

ACKR2 p.Trp169Ser

c.506G>C · rs2528588326 · VCV2242567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6566 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6566	likely pathogenic · top 9% in ACKR2
REVEL	0.653	pathogenic-leaning
SaProt	LLR -12.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,151 bp · p 0.35 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ACKR2
Protein: p.Trp169Ser
Coding: c.506G>C
MANE Select: NM_001296
dbSNP: rs2528588326
Type: single nucleotide variant
Location: chr3:42865008 (GRCh38)
Gene constraint: LOEUF 1.934 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 80.89 · 3 PDB
Residue 169: a disulfide bond

Full ACKR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCR10 p.Leu267Met Uncertain significance ★★ ⚠ same type
CCR10 p.Pro155= Benign ★★ same type
CCR9 p.Leu136= Benign ★★ same type
ACKR2 p.Ala248Thr Uncertain significance ★ ⚠ same type
ACKR2 p.Cys284Arg Uncertain significance ★ same type
ACKR2 p.His317Tyr Uncertain significance ★ ⚠ same type
ACKR2 p.Ile56Val Uncertain significance ★ ⚠ same type
ACKR2 p.Leu59Trp 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/ackr2-p-trp169ser (accessed [today's date]).

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