Is CCL26 p.Met2Val (c.4A>G) pathogenic?

CCL26 p.Met2Val (c.4A>G) is classified Uncertain significance in CCL26 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.1048); Very rare (popmax 0.00488%, eas).

How common is CCL26 p.Met2Val (c.4A>G) in the general population?

CCL26 p.Met2Val (c.4A>G) is very rare (popmax 0.00488%, eas) (gnomAD).

What do computational predictors say about CCL26 p.Met2Val (c.4A>G)?

AlphaMissense predicts likely benign (score 0.1048) — an in-silico prediction, not a clinical call.

CCL26 p.Met2Val

c.4A>G · VCV3487278

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1048 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00488%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1048	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.39	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 0.38	GERP 0.76, phastCons 0.22
Regional constraint	o/e 1.05	unconstrained · MANE · 2,480 bp · p 0.63 · regional, not allelic
Overall
CADD	7.377	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 0.00488% East Asian · 2/40,942 alleles

Filtering AF 0.0023% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00204%

Overall 0.00264% 41/1,550,660 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00488%	20,471
Remaining individualsnot grpmax-eligible	0.00333%	30,006
European (non-Finnish)	0.00314%	31,860
South Asian	0.00119%	84,166

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: CCL26
Protein: p.Met2Val
Coding: c.4A>G
MANE Select: NM_001371938
Type: single nucleotide variant
Location: chr7:75772173 (GRCh38)
Gene constraint: LOEUF 1.782 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.46 · 2 PDB

Full CCL26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL26 p.Met2Ile Uncertain significance ★ ⚠ same residue
CCL26 p.Arg60Trp Uncertain significance ★ ⚠ same type
CCL26 p.His39Gln Uncertain significance ★ ⚠ same type
CCL26 p.Leu42Ile Uncertain significance ★ ⚠ same type
CCL26 p.Lys92Thr Uncertain significance ★ ⚠ same type
CCL26 p.Ser27Ile Uncertain significance ★ ⚠ same type
CCL26 p.Ser30Phe Uncertain significance ★ ⚠ same type
CCL26 p.Thr45Ile 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/ccl26-p-met2val (accessed [today's date]).

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