Is CCR6 p.Pro50Leu (c.149C>T) pathogenic?

CCR6 p.Pro50Leu (c.149C>T) is classified Uncertain significance in CCR6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely pathogenic (0.8715); Very rare (popmax 0.0022%, sas).

How common is CCR6 p.Pro50Leu (c.149C>T) in the general population?

CCR6 p.Pro50Leu (c.149C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CCR6 p.Pro50Leu (c.149C>T)?

AlphaMissense predicts likely pathogenic (score 0.8715) — an in-silico prediction, not a clinical call.

CCR6 p.Pro50Leu

c.149C>T · rs1224171378 · VCV2485983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8715 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8715	likely pathogenic
REVEL	0.354	indeterminate
SaProt	LLR -17.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.46, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 1,217 bp · p 6e-11 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0022% South Asian · 2/91,072 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000547% 8/1,461,862 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Finnishnot grpmax-eligible	0.00312%	32,013
South Asiangrpmax	0.0022%	45,536
European (non-Finnish)	0.000254%	393,340

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: CCR6
Protein: p.Pro50Leu
Coding: c.149C>T
MANE Select: NM_031409
dbSNP: rs1224171378
Type: single nucleotide variant
Location: chr6:167136379 (GRCh38)
Gene constraint: LOEUF 1.538 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 79.56 · 1 PDB
Residue 50: an α-helix

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

Similar variants

CCR6 p.Pro50= Likely benign ★ same residue
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

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-pro50leu (accessed [today's date]).

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