Is CCL16 p.Leu93Pro (c.278T>C) pathogenic?

CCL16 p.Leu93Pro (c.278T>C) is classified Uncertain significance in CCL16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). AlphaMissense: likely pathogenic (0.7533); Absent from gnomAD v4.1.

How common is CCL16 p.Leu93Pro (c.278T>C) in the general population?

CCL16 p.Leu93Pro (c.278T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCL16 p.Leu93Pro (c.278T>C)?

AlphaMissense predicts likely pathogenic (score 0.7533) — an in-silico prediction, not a clinical call.

CCL16 p.Leu93Pro

c.278T>C · VCV4649931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7533 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7533	likely pathogenic · top 7% in CCL16
REVEL	0.152	moderately benign-leaning
SaProt	LLR -11.77	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 6.4	GERP 1.7, phastCons 0.86
Regional constraint	o/e 0.94	unconstrained · MANE · 3,851 bp · p 0.46 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCL16
Protein: p.Leu93Pro
Coding: c.278T>C
MANE Select: NM_004590
Type: single nucleotide variant
Location: chr17:35977651 (GRCh38)
Gene constraint: LOEUF 1.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.62 · 3 PDB

Full CCL16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL16 p.Ala64Thr Uncertain significance ★ ⚠ same type
CCL16 p.Asp82Asn Uncertain significance ★ ⚠ same type
CCL16 p.Asp82Gly Uncertain significance ★ ⚠ same type
CCL16 p.Glu5Lys Uncertain significance ★ ⚠ same type
CCL16 p.Glu74Ala Uncertain significance ★ ⚠ same type
CCL16 p.Gly112Val Uncertain significance ★ ⚠ same type
CCL16 p.Gly53Glu Uncertain significance ★ ⚠ same type
CCL16 p.Leu13Phe 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/ccl16-p-leu93pro (accessed [today's date]).

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