Is CCNL2 p.Ser67= (c.201C>T) pathogenic?

CCNL2 p.Ser67= (c.201C>T) is classified Likely benign in CCNL2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-10). Ultra-rare (popmax 0.015%, amr); Associated with CCNL2-related disorder.

What condition is associated with CCNL2 p.Ser67= (c.201C>T)?

CCNL2 p.Ser67= (c.201C>T) is associated with CCNL2-related disorder (ClinVar).

How common is CCNL2 p.Ser67= (c.201C>T) in the general population?

CCNL2 p.Ser67= (c.201C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

CCNL2 p.Ser67=

c.201C>T · rs764251755 · VCV3033974

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Conditions

CCNL2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP -0.78, phastCons 0.94
Overall
CADD	10.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/59,954 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00199% 32/1,611,694 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,662
European (non-Finnish)	0.00187%	53,610
Remaining individualsnot grpmax-eligible	0.0016%	62,394

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.Ser67=
Coding: c.201C>T
MANE Select: NM_030937
dbSNP: rs764251755
Type: single nucleotide variant
Location: chr1:1399106 (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

Disease context

CCNL2-related disorder

Similar variants

CCNL2 c.*4G>A Benign same condition
CCNL2 p.Arg40= Likely benign same condition
CCNL2 p.Ser25Cys Likely benign ⚠ same condition
CCNL2 p.Ser327= Likely benign same condition
CCNL2 p.Ser330= Likely benign same condition
CCNL2 c.473+10_473+13del Likely benign same condition
CCNL2 c.474-6del Likely benign same condition
CCNL2 p.Arg476Trp 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-ser67 (accessed [today's date]).

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