Is CCNL2 p.Glu306Ala (c.917A>C) pathogenic?

CCNL2 p.Glu306Ala (c.917A>C) is classified Uncertain significance in CCNL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-30). AlphaMissense: likely benign (0.111); Absent from gnomAD v4.1.

How common is CCNL2 p.Glu306Ala (c.917A>C) in the general population?

CCNL2 p.Glu306Ala (c.917A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNL2 p.Glu306Ala (c.917A>C)?

AlphaMissense predicts likely benign (score 0.111) — an in-silico prediction, not a clinical call.

CCNL2 p.Glu306Ala

c.917A>C · rs2523448210 · VCV2309337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.111 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.111	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -4.19	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 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,554 bp · p 0.19 · regional, not allelic
Overall
CADD	21.9	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

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: CCNL2
Protein: p.Glu306Ala
Coding: c.917A>C
MANE Select: NM_030937
dbSNP: rs2523448210
Type: single nucleotide variant
Location: chr1:1390319 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06 · 4 PDB

Full CCNL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNL2 p.Glu306Lys Uncertain significance ★ ⚠ same residue
CCNL2 p.Arg476Trp Uncertain significance ★★ ⚠ same type
CCNL2 p.Ala10Thr Uncertain significance ★ ⚠ same type
CCNL2 p.Ala18Thr Uncertain significance ★ ⚠ same type
CCNL2 p.Ala19Ser Uncertain significance ★ ⚠ same type
CCNL2 p.Ala22Ser Uncertain significance ★ ⚠ same type
CCNL2 p.Ala310Val Uncertain significance ★ ⚠ same type
CCNL2 p.Ala332Val 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/ccnl2-p-glu306ala (accessed [today's date]).

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