Is CCL8 p.Ile30Phe (c.88A>T) pathogenic?

CCL8 p.Ile30Phe (c.88A>T) is classified Uncertain significance in CCL8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.1033); Ultra-rare (popmax 0.049%, eas).

How common is CCL8 p.Ile30Phe (c.88A>T) in the general population?

CCL8 p.Ile30Phe (c.88A>T) is ultra-rare (popmax 0.049%, eas) (gnomAD).

What do computational predictors say about CCL8 p.Ile30Phe (c.88A>T)?

AlphaMissense predicts likely benign (score 0.1033) — an in-silico prediction, not a clinical call.

CCL8 p.Ile30Phe

c.88A>T · rs769159848 · VCV2341135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1033 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1033	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -8.49	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 0.29	GERP -3.8
Regional constraint	o/e 1.08	unconstrained · MANE · 1,402 bp · p 0.41 · regional, not allelic
Overall
CADD	14.2	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 0.049% East Asian · 22/44,854 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00273% 44/1,611,944 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.049%	2,039
South Asian	0.0187%	5,355
Remaining individualsnot grpmax-eligible	0.0032%	31,207
European (non-Finnish)	0.000255%	392,716

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: CCL8
Protein: p.Ile30Phe
Coding: c.88A>T
MANE Select: NM_005623
dbSNP: rs769159848
Type: single nucleotide variant
Location: chr17:34320280 (GRCh38)
Gene constraint: LOEUF 1.794 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 3 PDB

Full CCL8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL8 p.Ala14Val Benign ★★ same type
CCL8 p.Ile57= Benign ★★ same type
CCL8 p.Leu8= Benign ★★ same type
CCL8 p.Ser29= Benign ★★ same type
CCL8 p.Ala15Val Uncertain significance ★ ⚠ same type
CCL8 p.Ala23Ser Uncertain significance ★ ⚠ same type
CCL8 p.Ala5Thr Uncertain significance ★ ⚠ same type
CCL8 p.Arg53Gly 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/ccl8-p-ile30phe (accessed [today's date]).

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