Is ACKR5 p.Arg84Trp (c.250C>T) pathogenic?

ACKR5 p.Arg84Trp (c.250C>T) is classified Uncertain significance in ACKR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-03). AlphaMissense: likely benign (0.1124); Very rare (popmax 0.00223%, eas).

How common is ACKR5 p.Arg84Trp (c.250C>T) in the general population?

ACKR5 p.Arg84Trp (c.250C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ACKR5 p.Arg84Trp (c.250C>T)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

ACKR5 p.Arg84Trp

c.250C>T · rs778075996 · VCV2275769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -9.11	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 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 1,211 bp · p 0.45 · regional, not allelic
Overall
CADD	24.4	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 0.00223% East Asian · 1/44,878 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000547% 8/1,461,880 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
South Asian	0.0022%	45,546
African / African-American	0.00133%	75,044
European (non-Finnish)	0.000339%	295,008

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: ACKR5
Protein: p.Arg84Trp
Coding: c.250C>T
MANE Select: NM_007264
dbSNP: rs778075996
Type: single nucleotide variant
Location: chr12:56995459 (GRCh38)
Structure: AlphaFold pLDDT 79.73

Full ACKR5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACKR5 p.Thr210= Benign ★★ same type
GPR182 p.Ser181= Benign ★★ same type
ACKR5 p.Ala371Gly Uncertain significance ★ ⚠ same type
ACKR5 p.Arg254Trp Uncertain significance ★ ⚠ same type
ACKR5 p.Arg53Cys Uncertain significance ★ ⚠ same type
ACKR5 p.Arg53His Uncertain significance ★ ⚠ same type
ACKR5 p.Arg80Ser Uncertain significance ★ ⚠ same type
ACKR5 p.Glu188Lys 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/ackr5-p-arg84trp (accessed [today's date]).

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