Is CCR7 p.Met64Val (c.190A>G) pathogenic?

CCR7 p.Met64Val (c.190A>G) is classified Uncertain significance in CCR7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.1059); Very rare (popmax 0.00267%, afr).

How common is CCR7 p.Met64Val (c.190A>G) in the general population?

CCR7 p.Met64Val (c.190A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CCR7 p.Met64Val (c.190A>G)?

AlphaMissense predicts likely benign (score 0.1059) — an in-silico prediction, not a clinical call.

CCR7 p.Met64Val

c.190A>G · rs768527003 · VCV2227041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1059 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1059	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -4.72	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 2.9	GERP -0.23, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 11 kb · p 1.4e-10 · regional, not allelic
Overall
CADD	14.25	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 0.00267% African / African-American · 2/74,908 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,008 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: CCR7
Protein: p.Met64Val
Coding: c.190A>G
MANE Select: NM_001838
dbSNP: rs768527003
Type: single nucleotide variant
Location: chr17:40555689 (GRCh38)
Gene constraint: LOEUF 0.66 · pLI 0.40 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 7 PDB
Residue 64: an α-helix

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-met64val (accessed [today's date]).

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