Is CCL15 p.Lys68Arg (c.203A>G) pathogenic?

CCL15 p.Lys68Arg (c.203A>G) is classified Uncertain significance in CCL15 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-23). AlphaMissense: likely benign (0.0974); Very rare (popmax 0.00891%, eas).

How common is CCL15 p.Lys68Arg (c.203A>G) in the general population?

CCL15 p.Lys68Arg (c.203A>G) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CCL15 p.Lys68Arg (c.203A>G)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

CCL15 p.Lys68Arg

c.203A>G · rs567687330 · VCV2254496

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9
Overall
CADD	1.479	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00031% 5/1,614,186 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
Admixed American	0.00167%	60,022

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: CCL15
Protein: p.Lys68Arg
Coding: c.203A>G
MANE Select: NM_032965
dbSNP: rs567687330
Type: single nucleotide variant
Location: chr17:35998325 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 3 PDB
Residue 68: a β-strand; a disulfide bond

Full CCL15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL15 p.Ala15Gly Uncertain significance ★ ⚠ same type
CCL15 p.Arg90Trp Uncertain significance ★ ⚠ same type
CCL15 p.Cys77Ser Uncertain significance ★ ⚠ same type
CCL15 p.Ile113Thr Uncertain significance ★ ⚠ same type
CCL15 p.Ile113Val Uncertain significance ★ ⚠ same type
CCL15 p.Leu66Arg Uncertain significance ★ ⚠ same type
CCL15 p.Lys106Gln Uncertain significance ★ ⚠ same type
CCL15 p.Met33Thr 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/ccl15-p-lys68arg (accessed [today's date]).

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