Is CCL23 p.Arg108Pro (c.323G>C) pathogenic?

CCL23 p.Arg108Pro (c.323G>C) is classified Uncertain significance in CCL23 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: likely pathogenic (0.8764); Very rare (popmax 0.00935%, afr).

How common is CCL23 p.Arg108Pro (c.323G>C) in the general population?

CCL23 p.Arg108Pro (c.323G>C) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about CCL23 p.Arg108Pro (c.323G>C)?

AlphaMissense predicts likely pathogenic (score 0.8764) — an in-silico prediction, not a clinical call.

CCL23 p.Arg108Pro

c.323G>C · rs746038053 · VCV2207294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8764 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8764	likely pathogenic · top 7% in CCL23
REVEL	0.096	moderately benign-leaning
SaProt	LLR -13.28	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.8
Overall
CADD	14.43	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R91P vs ClinVar R108P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,890 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000558% 9/1,613,274 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,699
Admixed American	0.00167%	59,970
Remaining individualsnot grpmax-eligible	0.0016%	62,456

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: CCL23
Protein: p.Arg108Pro
Coding: c.323G>C
MANE Select: NM_005064
dbSNP: rs746038053
Type: single nucleotide variant
Location: chr17:36013288 (GRCh38)
Gene constraint: LOEUF 1.412 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75 · 1 PDB
Residue 108: an α-helix

Full CCL23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL23 p.Ala66Val Uncertain significance ★ ⚠ same type
CCL23 p.Ala6Thr Uncertain significance ★ ⚠ same type
CCL23 p.Arg131Gln Uncertain significance ★ ⚠ same type
CCL23 p.Arg78Gln Uncertain significance ★ ⚠ same type
CCL23 p.Asp70Asn Uncertain significance ★ ⚠ same type
CCL23 p.Gln118Lys Uncertain significance ★ ⚠ same type
CCL23 p.Glu30Lys Uncertain significance ★ ⚠ same type
CCL23 p.His60Gln 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/ccl23-p-arg108pro (accessed [today's date]).

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