Is CCM2L p.Ala299Ser (c.895G>T) pathogenic?

CCM2L p.Ala299Ser (c.895G>T) is classified Uncertain significance in CCM2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.1386); Absent from gnomAD v4.1.

How common is CCM2L p.Ala299Ser (c.895G>T) in the general population?

CCM2L p.Ala299Ser (c.895G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCM2L p.Ala299Ser (c.895G>T)?

AlphaMissense predicts likely benign (score 0.1386) — an in-silico prediction, not a clinical call.

CCM2L p.Ala299Ser

c.895G>T · VCV3487304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1386 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,521,596)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1386	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -3.96	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 11	GERP 1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 21 kb · p 8.3e-05 · regional, not allelic
Overall
CADD	24.7	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

No allele count reported in gnomAD v4.1 (AN 1,521,596). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCM2L
Protein: p.Ala299Ser
Coding: c.895G>T
MANE Select: NM_001365692
Type: single nucleotide variant
Location: chr20:32019371 (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.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
CCM2L p.Arg26Cys 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-ala299ser (accessed [today's date]).

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