Is CCL3 p.Arg68Gln (c.203G>A) pathogenic?

CCL3 p.Arg68Gln (c.203G>A) is classified Uncertain significance in CCL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.1688); Very rare (popmax 0.005%, amr).

How common is CCL3 p.Arg68Gln (c.203G>A) in the general population?

CCL3 p.Arg68Gln (c.203G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CCL3 p.Arg68Gln (c.203G>A)?

AlphaMissense predicts likely benign (score 0.1688) — an in-silico prediction, not a clinical call.

CCL3 p.Arg68Gln

c.203G>A · rs773703371 · VCV2591827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1688 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1688	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -10.91	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11
Overall
CADD	9.935	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 0.005% Admixed American · 3/59,996 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000868% 14/1,613,772 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,868
Admixed Americangrpmax	0.005%	19,999
Remaining individualsnot grpmax-eligible	0.0032%	31,233
African / African-American	0.00134%	74,888
European (non-Finnish)	0.000424%	235,978

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCL3
Protein: p.Arg68Gln
Coding: c.203G>A
MANE Select: NM_002983
dbSNP: rs773703371
Type: single nucleotide variant
Location: chr17:36088748 (GRCh38)
Gene constraint: LOEUF 1.346 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.58 · 13 PDB
Residue 68: a β-strand; a functional site (involved in gag binding); a disulfide bond

Full CCL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL3 p.Ala27Pro Uncertain significance ★ ⚠ same type
CCL3 p.Arg40Trp Uncertain significance ★ ⚠ same type
CCL3 p.Cys18Tyr Uncertain significance ★ ⚠ same type
CCL3 p.Gly61Val Uncertain significance ★ ⚠ same type
CCL3 p.Pro30Leu Uncertain significance ★ ⚠ same type
CCL3 p.Thr53Met Uncertain significance ★ ⚠ same type
CCL3 p.Tyr50Cys Uncertain significance ★ ⚠ same type
CCL3 p.Val62Ile 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/ccl3-p-arg68gln (accessed [today's date]).

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