Is CCL15 p.Cys77Ser (c.230G>C) pathogenic?

CCL15 p.Cys77Ser (c.230G>C) is classified Uncertain significance in CCL15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely pathogenic (0.9641); Very rare (popmax 0.00246%, nfe).

How common is CCL15 p.Cys77Ser (c.230G>C) in the general population?

CCL15 p.Cys77Ser (c.230G>C) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about CCL15 p.Cys77Ser (c.230G>C)?

AlphaMissense predicts likely pathogenic (score 0.9641) — an in-silico prediction, not a clinical call.

CCL15 p.Cys77Ser

c.230G>C · VCV4649926

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9641 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9641	likely pathogenic · top 1% in CCL15
REVEL	0.678	pathogenic-leaning
SaProt	LLR -10.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	phastCons 1
Overall
CADD	24.1	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

Grpmax group 0.00246% European (non-Finnish) · 29/1,179,314 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00192% 31/1,613,218 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,666
Remaining individualsnot grpmax-eligible	0.0016%	62,456
African / African-American	0.00133%	74,920

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.Cys77Ser
Coding: c.230G>C
MANE Select: NM_032965
Type: single nucleotide variant
Location: chr17:35998298 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 3 PDB
Residue 77: 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.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.Lys68Arg 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-cys77ser (accessed [today's date]).

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