Is CCL23 p.Ser74Pro (c.220T>C) pathogenic?

CCL23 p.Ser74Pro (c.220T>C) is classified Uncertain significance in CCL23 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: ambiguous (0.486); Ultra-rare (popmax 0.0493%, mid).

How common is CCL23 p.Ser74Pro (c.220T>C) in the general population?

CCL23 p.Ser74Pro (c.220T>C) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about CCL23 p.Ser74Pro (c.220T>C)?

AlphaMissense predicts ambiguous (score 0.486) — an in-silico prediction, not a clinical call.

CCL23 p.Ser74Pro

c.220T>C · rs151273610 · VCV2226679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.486 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.486	ambiguous
REVEL	0.108	moderately benign-leaning
SaProt	LLR -13.12	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3
Overall
CADD	10.79	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 S57P vs ClinVar S74P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,082 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00716%

Overall 0.0044% 71/1,614,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,027
European (non-Finnish)	0.00542%	18,437
Admixed American	0.00333%	30,006
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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.Ser74Pro
Coding: c.220T>C
MANE Select: NM_005064
dbSNP: rs151273610
Type: single nucleotide variant
Location: chr17:36013826 (GRCh38)
Gene constraint: LOEUF 1.412 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75 · 1 PDB
Residue 74: a disulfide bond

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

Similar variants

CCL23 p.Ser74Thr Uncertain significance ★ ⚠ same residue
CCL23 p.Ala66Val Uncertain significance ★ ⚠ same type
CCL23 p.Ala6Thr Uncertain significance ★ ⚠ same type
CCL23 p.Arg108Pro 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

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-ser74pro (accessed [today's date]).

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