Is CCL28 p.Val13Asp (c.38T>A) pathogenic?

CCL28 p.Val13Asp (c.38T>A) is classified Uncertain significance in CCL28 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely pathogenic (0.7128); Ultra-rare (popmax 0.0133%, amr).

How common is CCL28 p.Val13Asp (c.38T>A) in the general population?

CCL28 p.Val13Asp (c.38T>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about CCL28 p.Val13Asp (c.38T>A)?

AlphaMissense predicts likely pathogenic (score 0.7128) — an in-silico prediction, not a clinical call.

CCL28 p.Val13Asp

c.38T>A · rs748391100 · VCV3139748

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7128 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7128	likely pathogenic
REVEL	0.19	benign-leaning
SaProt	LLR -16.97	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 2.9	GERP -1.4, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 30 kb · p 0.33 · regional, not allelic
Overall
CADD	19.24	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

Grpmax group 0.0133% Admixed American · 8/59,956 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000496% 8/1,612,854 alleles · ultra-rare

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: CCL28
Protein: p.Val13Asp
Coding: c.38T>A
MANE Select: NM_148672
dbSNP: rs748391100
Type: single nucleotide variant
Location: chr5:43412279 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 72.76 · 1 PDB

Full CCL28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL28 p.Ala7Thr Uncertain significance ★ ⚠ same type
CCL28 p.Arg50Cys Uncertain significance ★ ⚠ same type
CCL28 p.Arg50His Uncertain significance ★ ⚠ same type
CCL28 p.Arg69Cys Uncertain significance ★ ⚠ same type
CCL28 p.Arg69Leu Uncertain significance ★ ⚠ same type
CCL28 p.Arg70Gly Uncertain significance ★ ⚠ same type
CCL28 p.Asp59Asn Uncertain significance ★ ⚠ same type
CCL28 p.Cys73Ser 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/ccl28-p-val13asp (accessed [today's date]).

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