Is CCL23 p.Phe102Leu (c.304T>C) pathogenic?

CCL23 p.Phe102Leu (c.304T>C) is classified Uncertain significance in CCL23 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely pathogenic (0.9214); Ultra-rare (popmax 0.0761%, afr).

How common is CCL23 p.Phe102Leu (c.304T>C) in the general population?

CCL23 p.Phe102Leu (c.304T>C) is ultra-rare (popmax 0.0761%, afr) (gnomAD).

What do computational predictors say about CCL23 p.Phe102Leu (c.304T>C)?

AlphaMissense predicts likely pathogenic (score 0.9214) — an in-silico prediction, not a clinical call.

CCL23 p.Phe102Leu

c.304T>C · VCV4649938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9214 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0761%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9214	likely pathogenic · top 4% in CCL23
REVEL	0.228	benign-leaning
SaProt	LLR -10.62	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 4.7	phastCons 1
Overall
CADD	24.0	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 F85L vs ClinVar F102L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0761% African / African-American · 57/74,950 alleles

Filtering AF 0.0602% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0545%

Overall 0.00442% 71/1,607,802 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0761%	1,315
Middle Eastern	0.0496%	2,016
Admixed American	0.00834%	11,985
Remaining individualsnot grpmax-eligible	0.00803%	12,457
European (non-Finnish)	8.51e-05%	1,174,491

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.Phe102Leu
Coding: c.304T>C
MANE Select: NM_005064
Type: single nucleotide variant
Location: chr17:36013307 (GRCh38)
Gene constraint: LOEUF 1.412 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75 · 1 PDB
Residue 102: an α-helix; a disulfide bond

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.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
CCL23 p.Glu30Lys 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-phe102leu (accessed [today's date]).

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