Is CXCR6 p.Phe80Ser (c.239T>C) pathogenic?

CXCR6 p.Phe80Ser (c.239T>C) is classified Uncertain significance in CXCR6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-29). AlphaMissense: likely pathogenic (0.8813); Absent from gnomAD v4.1.

How common is CXCR6 p.Phe80Ser (c.239T>C) in the general population?

CXCR6 p.Phe80Ser (c.239T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CXCR6 p.Phe80Ser (c.239T>C)?

AlphaMissense predicts likely pathogenic (score 0.8813) — an in-silico prediction, not a clinical call.

CXCR6 p.Phe80Ser

c.239T>C · VCV3498872

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8813 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8813	likely pathogenic · top 4% in CXCR6
REVEL	0.884	moderately pathogenic-leaning
SaProt	LLR -12.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 1,025 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	26.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CXCR6
Protein: p.Phe80Ser
Coding: c.239T>C
MANE Select: NM_006564
Type: single nucleotide variant
Location: chr3:45946720 (GRCh38)
Gene constraint: LOEUF 1.476 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.16

Full CXCR6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CXCR6 p.Asp184= Benign/Likely benign ★★ same type
CXCR6 p.Asp77= Likely benign ★★ same type
CXCR6 p.Phe234= Benign ★★ same type
CXCR6 p.Ala221Thr Uncertain significance ★ ⚠ same type
CXCR6 p.Arg127His Uncertain significance ★ ⚠ same type
CXCR6 p.Arg254Cys Uncertain significance ★ ⚠ same type
CXCR6 p.Asn333Ser Uncertain significance ★ ⚠ same type
CXCR6 p.Asp323Glu 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/cxcr6-p-phe80ser (accessed [today's date]).

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