Is CCR6 p.Arg159= (c.477A>G) pathogenic?

CCR6 p.Arg159= (c.477A>G) is classified Benign in CCR6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-01). Low-frequency (popmax 1.15%, nfe).

How common is CCR6 p.Arg159= (c.477A>G) in the general population?

CCR6 p.Arg159= (c.477A>G) is low-frequency (popmax 1.15%, nfe) (gnomAD).

CCR6 p.Arg159=

c.477A>G · rs41510645 · VCV717856

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -2.1
Overall
CADD	0.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.15% European (non-Finnish) · 13,557/1,180,030 alleles

Filtering AF 1.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.13%

Overall 0.972% 15,690/1,614,092 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.06%	49
European (non-Finnish)grpmax	1.15%	87
Remaining individualsnot grpmax-eligible	0.768%	130
Amishnot grpmax-eligible	0.658%	152
Admixed American	0.172%	583
African / African-American	0.165%	605
South Asian	0.105%	949
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401

Finnish 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: CCR6
Protein: p.Arg159=
Coding: c.477A>G
MANE Select: NM_031409
dbSNP: rs41510645
Type: single nucleotide variant
Location: chr6:167136707 (GRCh38)
Gene constraint: LOEUF 1.538 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 79.56 · 1 PDB
Residue 159: a disulfide bond

Full CCR6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCR6 p.Ala369Val Benign/Likely benign ★★ same type
CCR6 p.Ala110Val Uncertain significance ★ ⚠ same type
CCR6 p.Ala265Thr Uncertain significance ★ ⚠ same type
CCR6 p.Ala265Val Uncertain significance ★ ⚠ same type
CCR6 p.Ala364Thr Uncertain significance ★ ⚠ same type
CCR6 p.Arg157Gln Uncertain significance ★ ⚠ same type
CCR6 p.Arg163Ser Uncertain significance ★ ⚠ same type
CCR6 p.Gln39Arg 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/ccr6-p-arg159 (accessed [today's date]).

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