Is CCR7 p.Lys339Arg (c.1016A>G) pathogenic?

CCR7 p.Lys339Arg (c.1016A>G) is classified Uncertain significance in CCR7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0805); Ultra-rare (popmax 0.0242%, nfe).

How common is CCR7 p.Lys339Arg (c.1016A>G) in the general population?

CCR7 p.Lys339Arg (c.1016A>G) is ultra-rare (popmax 0.0242%, nfe) (gnomAD).

What do computational predictors say about CCR7 p.Lys339Arg (c.1016A>G)?

AlphaMissense predicts likely benign (score 0.0805) — an in-silico prediction, not a clinical call.

CCR7 p.Lys339Arg

c.1016A>G · rs148614545 · VCV2397191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0805 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0805	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -5.72	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 5.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 11 kb · p 1.4e-10 · regional, not allelic
Overall
CADD	20.6	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 0.0242% European (non-Finnish) · 286/1,180,028 alleles

Filtering AF 0.0219% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.0185% 298/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0242%	4,126
Remaining individualsnot grpmax-eligible	0.0144%	6,943
African / African-American	0.004%	24,972

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: CCR7
Protein: p.Lys339Arg
Coding: c.1016A>G
MANE Select: NM_001838
dbSNP: rs148614545
Type: single nucleotide variant
Location: chr17:40554863 (GRCh38)
Gene constraint: LOEUF 0.66 · pLI 0.40 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 7 PDB

Full CCR7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCR7 p.Arg154= Benign ★★ same type
CCR7 p.Ala261Ser Uncertain significance ★ ⚠ same type
CCR7 p.Ala307Thr Uncertain significance ★ ⚠ same type
CCR7 p.Ala327Thr Uncertain significance ★ ⚠ same type
CCR7 p.Ala58Gly Uncertain significance ★ ⚠ same type
CCR7 p.Arg170His Uncertain significance ★ ⚠ same type
CCR7 p.Arg248Leu Uncertain significance ★ ⚠ same type
CCR7 p.Arg318His 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/ccr7-p-lys339arg (accessed [today's date]).

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