Is ACKR2 p.Ser316Ile (c.947G>T) pathogenic?

ACKR2 p.Ser316Ile (c.947G>T) is classified Uncertain significance in ACKR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.2849); Rare (popmax 0.165%, mid).

How common is ACKR2 p.Ser316Ile (c.947G>T) in the general population?

ACKR2 p.Ser316Ile (c.947G>T) is rare (popmax 0.165%, mid) (gnomAD).

What do computational predictors say about ACKR2 p.Ser316Ile (c.947G>T)?

AlphaMissense predicts likely benign (score 0.2849) — an in-silico prediction, not a clinical call.

ACKR2 p.Ser316Ile

c.947G>T · rs184802180 · VCV2348773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2849 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2849	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -9.59	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 4.6	GERP -0.51, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,151 bp · p 0.35 · regional, not allelic
Overall
CADD	17.75	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 0.165% Middle Eastern · 10/6,062 alleles

Filtering AF 0.0895% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0681%

Overall 0.0144% 232/1,614,158 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.209%	478
Middle Easterngrpmax	0.165%	606
Admixed American	0.0483%	2,070
Remaining individualsnot grpmax-eligible	0.0368%	2,718
European (non-Finnish)	0.00873%	11,457
African / African-American	0.00533%	18,756
South Asian	0.0011%	91,080

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACKR2
Protein: p.Ser316Ile
Coding: c.947G>T
MANE Select: NM_001296
dbSNP: rs184802180
Type: single nucleotide variant
Location: chr3:42865449 (GRCh38)
Gene constraint: LOEUF 1.934 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 80.89 · 3 PDB

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

Similar variants

CCR10 p.Arg316Ser Uncertain significance ★ ⚠ same residue
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

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-ser316ile (accessed [today's date]).

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