Is CCM2 p.Arg390Gln (c.1169G>A) pathogenic?

CCM2 p.Arg390Gln (c.1169G>A) is classified Uncertain significance in CCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.2517); Very rare (popmax 0.00668%, eas); Associated with Inborn genetic diseases.

What condition is associated with CCM2 p.Arg390Gln (c.1169G>A)?

CCM2 p.Arg390Gln (c.1169G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CCM2 p.Arg390Gln (c.1169G>A) in the general population?

CCM2 p.Arg390Gln (c.1169G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about CCM2 p.Arg390Gln (c.1169G>A)?

AlphaMissense predicts likely benign (score 0.2517) — an in-silico prediction, not a clinical call.

CCM2 p.Arg390Gln

c.1169G>A · rs1469968795 · VCV3139756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2517 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2517	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -7.61	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 9.8	GERP 0.64, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 76 kb · p 3.5e-05 · regional, not allelic
Overall
CADD	23.9	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 0.00668% East Asian · 3/44,886 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00103% 15/1,460,978 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,962
African / African-American	0.004%	25,015
European (non-Finnish)	0.000763%	131,113

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: CCM2
Protein: p.Arg390Gln
Coding: c.1169G>A
MANE Select: NM_031443
dbSNP: rs1469968795
Type: single nucleotide variant
Location: chr7:45075891 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.48 · 8 PDB

Full CCM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCM2 p.Ala186Thr Uncertain significance ★★ ⚠ same condition
CCM2 p.Arg326His Uncertain significance ★★ ⚠ same condition
CCM2 p.Arg423Pro Uncertain significance ★★ ⚠ same condition
CCM2 p.Gln441Arg Uncertain significance ★★ ⚠ same condition
CCM2 p.Ile131Asn Uncertain significance ★★ ⚠ same condition
CCM2 p.Pro102Leu Uncertain significance ★★ ⚠ same condition
CCM2 p.Val374Met Uncertain significance ★★ ⚠ same condition
CCM2 p.Arg378= Likely benign ★★ same condition

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/ccm2-p-arg390gln (accessed [today's date]).

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