Is CCL28 p.Ala7Thr (c.19G>A) pathogenic?

CCL28 p.Ala7Thr (c.19G>A) is classified Uncertain significance in CCL28 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely benign (0.0728); Ultra-rare (popmax 0.066%, mid).

How common is CCL28 p.Ala7Thr (c.19G>A) in the general population?

CCL28 p.Ala7Thr (c.19G>A) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about CCL28 p.Ala7Thr (c.19G>A)?

AlphaMissense predicts likely benign (score 0.0728) — an in-silico prediction, not a clinical call.

CCL28 p.Ala7Thr

c.19G>A · VCV3997501

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0728 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0728	likely benign
REVEL	0.003	strongly benign-leaning
SaProt	LLR -7.69	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 -2.7	GERP -3.8
Regional constraint	o/e 0.92	unconstrained · MANE · 30 kb · p 0.33 · regional, not allelic
Overall
CADD	0.843	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 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.00415% 67/1,612,810 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
Admixed American	0.0484%	2,068
Remaining individualsnot grpmax-eligible	0.0144%	6,941
Finnishnot grpmax-eligible	0.0141%	7,091
East Asian	0.00223%	44,862
African / African-American	0.00133%	75,036
European (non-Finnish)	0.00119%	84,242

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.Ala7Thr
Coding: c.19G>A
MANE Select: NM_148672
Type: single nucleotide variant
Location: chr5:43412298 (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.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
CCL28 p.Gln2Leu 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-ala7thr (accessed [today's date]).

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