Is ACKR5 p.Pro200Ser (c.598C>T) pathogenic?

ACKR5 p.Pro200Ser (c.598C>T) is classified Uncertain significance in ACKR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.1924); Absent from gnomAD v4.1.

How common is ACKR5 p.Pro200Ser (c.598C>T) in the general population?

ACKR5 p.Pro200Ser (c.598C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACKR5 p.Pro200Ser (c.598C>T)?

AlphaMissense predicts likely benign (score 0.1924) — an in-silico prediction, not a clinical call.

ACKR5 p.Pro200Ser

c.598C>T · rs2547939282 · VCV3101645

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1924 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1924	likely benign
REVEL	0.516	indeterminate
SaProt	LLR -9.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 1,211 bp · p 0.45 · regional, not allelic
Overall
CADD	24.2	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

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: ACKR5
Protein: p.Pro200Ser
Coding: c.598C>T
MANE Select: NM_007264
dbSNP: rs2547939282
Type: single nucleotide variant
Location: chr12:56995807 (GRCh38)
Structure: AlphaFold pLDDT 79.73
Residue 200: a disulfide bond

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.Arg84Trp 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-pro200ser (accessed [today's date]).

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