Is CCL8 p.Ala14Val (c.41C>T) pathogenic?

CCL8 p.Ala14Val (c.41C>T) is classified Benign in CCL8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-29). AlphaMissense: likely benign (0.0988); Low-frequency (popmax 2.42%, afr).

How common is CCL8 p.Ala14Val (c.41C>T) in the general population?

CCL8 p.Ala14Val (c.41C>T) is low-frequency (popmax 2.42%, afr) (gnomAD).

What do computational predictors say about CCL8 p.Ala14Val (c.41C>T)?

AlphaMissense predicts likely benign (score 0.0988) — an in-silico prediction, not a clinical call.

CCL8 p.Ala14Val

c.41C>T · rs35401229 · VCV714732

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0988 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.42%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0988	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.40	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	GERP -2.6
Regional constraint	o/e 1.08	unconstrained · MANE · 1,402 bp · p 0.41 · regional, not allelic
Overall
CADD	1.138	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 2.42% African / African-American · 1,815/74,996 alleles

Filtering AF 2.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.29%

Overall 0.126% 2,039/1,613,840 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.42%	41
Remaining individualsnot grpmax-eligible	0.154%	651
Admixed American	0.142%	706
Middle Eastern	0.0991%	1,009
South Asian	0.00659%	15,180
European (non-Finnish)	0.00263%	38,059

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.Ala14Val
Coding: c.41C>T
MANE Select: NM_005623
dbSNP: rs35401229
Type: single nucleotide variant
Location: chr17:34319542 (GRCh38)
Gene constraint: LOEUF 1.794 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 89.44 · 3 PDB
Residue 14: a UniProt-annotated variant site (in)

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

Similar variants

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
CCL8 p.Asp85Tyr 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-ala14val (accessed [today's date]).

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