Is CCL4 p.Val86Met (c.256G>A) pathogenic?

CCL4 p.Val86Met (c.256G>A) is classified Likely benign in CCL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.1291); Very rare (popmax 0.00576%, nfe).

How common is CCL4 p.Val86Met (c.256G>A) in the general population?

CCL4 p.Val86Met (c.256G>A) is very rare (popmax 0.00576%, nfe) (gnomAD).

What do computational predictors say about CCL4 p.Val86Met (c.256G>A)?

AlphaMissense predicts likely benign (score 0.1291) — an in-silico prediction, not a clinical call.

CCL4 p.Val86Met

c.256G>A · rs374631046 · VCV3139751

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1291 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00576%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1291	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -8.02	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 -1.8
Regional constraint	o/e 0.95	unconstrained · MANE · 1,403 bp · p 0.62 · regional, not allelic
Overall
CADD	3.634	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 0.00576% European (non-Finnish) · 68/1,179,906 alleles

Filtering AF 0.00462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00423%

Overall 0.00459% 74/1,613,936 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00576%	17,352
Remaining individualsnot grpmax-eligible	0.0032%	31,243
South Asian	0.0022%	45,542
Admixed American	0.00167%	60,014
African / African-American	0.00134%	74,904

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: CCL4
Protein: p.Val86Met
Coding: c.256G>A
MANE Select: NM_002984
dbSNP: rs374631046
Type: single nucleotide variant
Location: chr17:36105289 (GRCh38)
Gene constraint: LOEUF 1.443 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.72 · 8 PDB
Residue 86: an α-helix

Full CCL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL4 p.Ala40Ser Uncertain significance ★ ⚠ same type
CCL4 p.Ala40Thr Uncertain significance ★ ⚠ same type
CCL4 p.Arg45Cys Uncertain significance ★ ⚠ same type
CCL4 p.Asp29Val Uncertain significance ★ same type
CCL4 p.Asp88Val Uncertain significance ★ ⚠ same type
CCL4 p.Cys4Trp Uncertain significance ★ ⚠ same type
CCL4 p.Gln66Glu Uncertain significance ★ ⚠ same type
CCL4 p.Leu43Val 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/ccl4-p-val86met (accessed [today's date]).

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