Is CCR6 p.Phe236Leu (c.706T>C) pathogenic?

CCR6 p.Phe236Leu (c.706T>C) is classified Uncertain significance in CCR6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: ambiguous (0.4847); Ultra-rare (popmax 0.0169%, nfe).

How common is CCR6 p.Phe236Leu (c.706T>C) in the general population?

CCR6 p.Phe236Leu (c.706T>C) is ultra-rare (popmax 0.0169%, nfe) (gnomAD).

What do computational predictors say about CCR6 p.Phe236Leu (c.706T>C)?

AlphaMissense predicts ambiguous (score 0.4847) — an in-silico prediction, not a clinical call.

CCR6 p.Phe236Leu

c.706T>C · VCV3487581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4847 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4847	ambiguous
REVEL	0.071	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.054	GERP -2.4
Regional constraint	o/e 0.70	unconstrained · MANE · 1,217 bp · p 6e-11 · regional, not allelic
Overall
CADD	4.239	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 0.0169% European (non-Finnish) · 199/1,180,032 alleles

Filtering AF 0.0149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0142%

Overall 0.0129% 209/1,614,190 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0169%	5,930
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Admixed American	0.00333%	30,007
African / African-American	0.00133%	75,050

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.Phe236Leu
Coding: c.706T>C
MANE Select: NM_031409
Type: single nucleotide variant
Location: chr6:167136936 (GRCh38)
Gene constraint: LOEUF 1.538 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 79.56 · 1 PDB
Residue 236: an α-helix

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.Arg159= 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

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-phe236leu (accessed [today's date]).

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