Is CXCL6 p.Arg48Pro (c.143G>C) pathogenic?

CXCL6 p.Arg48Pro (c.143G>C) is classified Uncertain significance in CXCL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely pathogenic (0.8166); Absent from gnomAD v4.1.

How common is CXCL6 p.Arg48Pro (c.143G>C) in the general population?

CXCL6 p.Arg48Pro (c.143G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CXCL6 p.Arg48Pro (c.143G>C)?

AlphaMissense predicts likely pathogenic (score 0.8166) — an in-silico prediction, not a clinical call.

CXCL6 p.Arg48Pro

c.143G>C · VCV4657833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8166 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8166	likely pathogenic · top 7% in CXCL6
REVEL	0.443	indeterminate
SaProt	LLR -13.96	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 887 bp · p 0.036 · regional, not allelic
Overall
CADD	30.0	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

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: CXCL6
Protein: p.Arg48Pro
Coding: c.143G>C
MANE Select: NM_002993
Type: single nucleotide variant
Location: chr4:73836997 (GRCh38)
Gene constraint: LOEUF 1.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.78 · 2 PDB

Full CXCL6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CXCL6 p.Arg53Leu Uncertain significance ★ ⚠ same type
CXCL6 p.Asn114Asp Uncertain significance ★ ⚠ same type
CXCL6 p.Cys75Arg Uncertain significance ★ ⚠ same type
CXCL6 p.Gly38Arg Uncertain significance ★ ⚠ same type
CXCL6 p.Gly38Val Uncertain significance ★ ⚠ same type
CXCL6 p.Leu21Gln Uncertain significance ★ ⚠ same type
CXCL6 p.Leu99Val Uncertain significance ★ ⚠ same type
CXCL6 p.Lys101Asn 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/cxcl6-p-arg48pro (accessed [today's date]).

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