Is CCM2L p.Asp449= (c.1347C>T) pathogenic?

CCM2L p.Asp449= (c.1347C>T) is classified Uncertain significance in CCM2L (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). Absent from gnomAD v4.1.

How common is CCM2L p.Asp449= (c.1347C>T) in the general population?

CCM2L p.Asp449= (c.1347C>T) is absent from gnomAD v4.1 (gnomAD).

CCM2L p.Asp449=

c.1347C>T · rs2064902888 · VCV2470615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.095	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.54	GERP -0.2, phastCons 1
Overall
CADD	6.964	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCM2L
Protein: p.Asp449=
Coding: c.1347C>T
MANE Select: NM_001365692
dbSNP: rs2064902888
Type: single nucleotide variant
Location: chr20:32029783 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.84

Full CCM2L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCM2L p.Ala183Glu Uncertain significance ★ ⚠ same type
CCM2L p.Ala214Gly Uncertain significance ★ ⚠ same type
CCM2L p.Ala299Ser Uncertain significance ★ ⚠ same type
CCM2L p.Ala435= Uncertain significance ★ same type
CCM2L p.Ala93Ser Uncertain significance ★ ⚠ same type
CCM2L p.Arg195Cys Uncertain significance ★ ⚠ same type
CCM2L p.Arg204Gln Uncertain significance ★ ⚠ same type
CCM2L p.Arg215Trp 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/ccm2l-p-asp449 (accessed [today's date]).

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