Is CCL4 p.Asp88Val (c.263A>T) pathogenic?

CCL4 p.Asp88Val (c.263A>T) is classified Uncertain significance in CCL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-21). AlphaMissense: ambiguous (0.3981); Very rare (popmax 0.000678%, nfe).

How common is CCL4 p.Asp88Val (c.263A>T) in the general population?

CCL4 p.Asp88Val (c.263A>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CCL4 p.Asp88Val (c.263A>T)?

AlphaMissense predicts ambiguous (score 0.3981) — an in-silico prediction, not a clinical call.

CCL4 p.Asp88Val

c.263A>T · rs781405487 · VCV2604714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3981	ambiguous
REVEL	0.24	benign-leaning
SaProt	LLR -11.44	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 1,403 bp · p 0.62 · regional, not allelic
Overall
CADD	21.9	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 0.000678% European (non-Finnish) · 8/1,179,796 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000547% 8/1,461,652 alleles · very rare

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.Asp88Val
Coding: c.263A>T
MANE Select: NM_002984
dbSNP: rs781405487
Type: single nucleotide variant
Location: chr17:36105296 (GRCh38)
Gene constraint: LOEUF 1.443 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.72 · 8 PDB
Residue 88: 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.Cys4Trp Uncertain significance ★ ⚠ same type
CCL4 p.Gln66Glu Uncertain significance ★ ⚠ same type
CCL4 p.Leu43Val Uncertain significance ★ ⚠ same type
CCL4 p.Phe17Leu 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-asp88val (accessed [today's date]).

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