Is ACKR1 p.Val115Ile (c.343G>A) pathogenic?

ACKR1 p.Val115Ile (c.343G>A) is classified Likely benign in ACKR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.0623); Very rare (popmax 0.00659%, sas).

How common is ACKR1 p.Val115Ile (c.343G>A) in the general population?

ACKR1 p.Val115Ile (c.343G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about ACKR1 p.Val115Ile (c.343G>A)?

AlphaMissense predicts likely benign (score 0.0623) — an in-silico prediction, not a clinical call.

ACKR1 p.Val115Ile

c.343G>A · VCV3998491

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0623 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0623	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.25	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 -0.62	GERP -4.1
Regional constraint	o/e 1.11	unconstrained · MANE · 1,487 bp · p 0.031 · regional, not allelic
Overall
CADD	0.199	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,076 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00149% 24/1,613,968 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,179
East Asian	0.00446%	22,445
Admixed American	0.00333%	30,005
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00133%	74,932
European (non-Finnish)	0.000932%	107,273

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.Val115Ile
Coding: c.343G>A
MANE Select: NM_002036
Type: single nucleotide variant
Location: chr1:159205782 (GRCh38)
Gene constraint: LOEUF 1.841 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 78.25 · 6 PDB
Residue 115: 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-val115ile (accessed [today's date]).

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