Is CCNL2 p.Ala6Val (c.17C>T) pathogenic?

CCNL2 p.Ala6Val (c.17C>T) is classified Uncertain significance in CCNL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). AlphaMissense: likely benign (0.2193); Ultra-rare (popmax 0.0634%, mid).

How common is CCNL2 p.Ala6Val (c.17C>T) in the general population?

CCNL2 p.Ala6Val (c.17C>T) is ultra-rare (popmax 0.0634%, mid) (gnomAD).

What do computational predictors say about CCNL2 p.Ala6Val (c.17C>T)?

AlphaMissense predicts likely benign (score 0.2193) — an in-silico prediction, not a clinical call.

CCNL2 p.Ala6Val

c.17C>T · VCV3829144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2193 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0634%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2193	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -9.73	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 1.1	GERP 1.6, phastCons 0.006
Regional constraint	o/e 1.06	unconstrained · MANE · 3,876 bp · p 0.35 · regional, not allelic
Overall
CADD	19.76	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 0.0634% Middle Eastern · 3/4,730 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00918%

Overall 0.00428% 62/1,450,186 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0634%	1,577
Remaining individualsnot grpmax-eligible	0.009%	11,109
European (non-Finnish)	0.0046%	21,743
African / African-American	0.003%	33,361
South Asian	0.00144%	69,434

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.Ala6Val
Coding: c.17C>T
MANE Select: NM_030937
Type: single nucleotide variant
Location: chr1:1399290 (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.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
CCNL2 p.Ala362Gly 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-ala6val (accessed [today's date]).

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