Is CCNL2 p.Arg387His (c.1160G>A) pathogenic?

CCNL2 p.Arg387His (c.1160G>A) is classified Uncertain significance in CCNL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-28). AlphaMissense: likely benign (0.0842); Very rare (popmax 0.00602%, nfe).

How common is CCNL2 p.Arg387His (c.1160G>A) in the general population?

CCNL2 p.Arg387His (c.1160G>A) is very rare (popmax 0.00602%, nfe) (gnomAD).

What do computational predictors say about CCNL2 p.Arg387His (c.1160G>A)?

AlphaMissense predicts likely benign (score 0.0842) — an in-silico prediction, not a clinical call.

CCNL2 p.Arg387His

c.1160G>A · VCV4650114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0842 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0842	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -9.41	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 1.4	GERP -0.99, phastCons 0.97
Regional constraint	o/e 1.07	unconstrained · MANE · 3,554 bp · p 0.19 · regional, not allelic
Overall
CADD	19.66	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 0.00602% European (non-Finnish) · 71/1,179,892 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00484% 78/1,613,164 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,618
South Asian	0.0044%	22,741
Admixed American	0.00167%	59,948
Finnishnot grpmax-eligible	0.00157%	63,612
African / African-American	0.00134%	74,848

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.Arg387His
Coding: c.1160G>A
MANE Select: NM_030937
Type: single nucleotide variant
Location: chr1:1387828 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06 · 4 PDB
Residue 387: the 'disordered' region; the 'rs' region

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-arg387his (accessed [today's date]).

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