Is CCL27 p.Ile78Val (c.232A>G) pathogenic?

CCL27 p.Ile78Val (c.232A>G) is classified Benign in CCL27 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-06). AlphaMissense: likely benign (0.1068); Common (popmax 8.84%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CCL27 p.Ile78Val (c.232A>G)?

AlphaMissense predicts likely benign (score 0.1068) — an in-silico prediction, not a clinical call.

CCL27 p.Ile78Val

Q: How common is CCL27 p.Ile78Val (c.232A>G) in the general population?

CCL27 p.Ile78Val (c.232A>G) is common (popmax 8.84%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.232A>G · rs11575594 · VCV768290

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1068 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.84%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1068	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -5.05	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 0.46	GERP -0.61, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 686 bp · p 1 · regional, not allelic
Overall
CADD	9.256	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 8.84% African / African-American · 6,630/75,038 alleles

Filtering AF 8.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.59%

Overall 0.478% 7,713/1,614,194 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.84%	11
Admixed American	0.718%	139
Remaining individualsnot grpmax-eligible	0.667%	150
Middle Eastern	0.462%	216
European (non-Finnish)	0.0166%	6,021
South Asian	0.0121%	8,281

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: CCL27
Protein: p.Ile78Val
Coding: c.232A>G
MANE Select: NM_006664
dbSNP: rs11575594
Type: single nucleotide variant
Location: chr9:34662051 (GRCh38)
Gene constraint: LOEUF 1.814 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.96 · 1 PDB
Residue 78: a β-strand; a UniProt-annotated variant site (in)

Full CCL27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL27 p.Arg109Trp Uncertain significance ★ ⚠ same type
CCL27 p.Cys34Tyr Uncertain significance ★ ⚠ same type
CCL27 p.Cys8Phe Uncertain significance ★ ⚠ same type
CCL27 p.Gln52Lys Uncertain significance ★ ⚠ same type
CCL27 p.Gly3Glu Uncertain significance ★ ⚠ same type
CCL27 p.Leu37Phe Uncertain significance ★ ⚠ same type
CCL27 p.Leu46Val Uncertain significance ★ ⚠ same type
CCL27 p.Leu64Arg 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/ccl27-p-ile78val (accessed [today's date]).

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