Is CCNL2 p.Ala18Thr (c.52G>A) pathogenic?

CCNL2 p.Ala18Thr (c.52G>A) is classified Uncertain significance in CCNL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.1167); Very rare (popmax 0.00559%, afr).

How common is CCNL2 p.Ala18Thr (c.52G>A) in the general population?

CCNL2 p.Ala18Thr (c.52G>A) is very rare (popmax 0.00559%, afr) (gnomAD).

What do computational predictors say about CCNL2 p.Ala18Thr (c.52G>A)?

AlphaMissense predicts likely benign (score 0.1167) — an in-silico prediction, not a clinical call.

CCNL2 p.Ala18Thr

c.52G>A · rs913480225 · VCV2616165

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1167 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00559%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1167	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -9.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 1.06	unconstrained · MANE · 3,876 bp · p 0.35 · regional, not allelic
Overall
CADD	14.69	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 0.00559% African / African-American · 4/71,508 alleles

Filtering AF 0.0019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.000568% 9/1,583,480 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00559%	17,877
Remaining individualsnot grpmax-eligible	0.00328%	30,489
European (non-Finnish)	0.000257%	389,390

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: CCNL2
Protein: p.Ala18Thr
Coding: c.52G>A
MANE Select: NM_030937
dbSNP: rs913480225
Type: single nucleotide variant
Location: chr1:1399255 (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.Arg476Trp Uncertain significance ★★ ⚠ same type
CCNL2 p.Ala10Thr 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
CCNL2 p.Ala362Gly Uncertain significance ★ ⚠ same type
CCNL2 p.Ala399Val 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-ala18thr (accessed [today's date]).

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