Is CCR6 p.Val83Phe (c.247G>T) pathogenic?

CCR6 p.Val83Phe (c.247G>T) is classified Uncertain significance in CCR6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.2836); Very rare (popmax 0.0087%, nfe).

How common is CCR6 p.Val83Phe (c.247G>T) in the general population?

CCR6 p.Val83Phe (c.247G>T) is very rare (popmax 0.0087%, nfe) (gnomAD).

What do computational predictors say about CCR6 p.Val83Phe (c.247G>T)?

AlphaMissense predicts likely benign (score 0.2836) — an in-silico prediction, not a clinical call.

CCR6 p.Val83Phe

c.247G>T · VCV4650218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2836 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0087%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2836	likely benign
REVEL	0.546	indeterminate
SaProt	LLR -7.92	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 4.7	GERP -1.9, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 1,217 bp · p 6e-11 · regional, not allelic
Overall
CADD	20.8	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 0.0087% European (non-Finnish) · 102/1,172,170 alleles

Filtering AF 0.00729% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0068%

Overall 0.00651% 104/1,598,522 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0087%	11,492
Remaining individualsnot grpmax-eligible	0.00324%	30,898

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.Val83Phe
Coding: c.247G>T
MANE Select: NM_031409
Type: single nucleotide variant
Location: chr6:167136477 (GRCh38)
Gene constraint: LOEUF 1.538 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 79.56 · 1 PDB
Residue 83: 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-val83phe (accessed [today's date]).

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