Is CCNB2 p.Arg164Cys (c.490C>T) pathogenic?

CCNB2 p.Arg164Cys (c.490C>T) is classified Uncertain significance in CCNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.3361); Rare (popmax 0.165%, mid).

How common is CCNB2 p.Arg164Cys (c.490C>T) in the general population?

CCNB2 p.Arg164Cys (c.490C>T) is rare (popmax 0.165%, mid) (gnomAD).

What do computational predictors say about CCNB2 p.Arg164Cys (c.490C>T)?

AlphaMissense predicts likely benign (score 0.3361) — an in-silico prediction, not a clinical call.

CCNB2 p.Arg164Cys

c.490C>T · rs144432316 · VCV2362204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3361 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3361	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 3.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 20 kb · p 0.94 · regional, not allelic
Overall
CADD	32.0	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 0.165% Middle Eastern · 10/6,060 alleles

Filtering AF 0.123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.121%

Overall 0.11% 1,769/1,614,048 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.189%	529
Middle Easterngrpmax	0.165%	606
European (non-Finnish)	0.129%	777
South Asian	0.0933%	1,072
Remaining individualsnot grpmax-eligible	0.0656%	1,524
Admixed American	0.0383%	2,609
African / African-American	0.036%	2,779
Finnishnot grpmax-eligible	0.0125%	8,002
East Asian	0.00223%	44,884

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCNB2
Protein: p.Arg164Cys
Coding: c.490C>T
MANE Select: NM_004701
dbSNP: rs144432316
Type: single nucleotide variant
Location: chr15:59114769 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.14

Full CCNB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNB2 p.Arg164His Uncertain significance ★ ⚠ same residue
CCNB2 p.Ile395Thr Benign ★★ same type
CCNB2 p.Lys89= Benign ★★ same type
CCNB2 p.Met100Thr Benign ★★ same type
CCNB2 p.Ala112Gly Uncertain significance ★ ⚠ same type
CCNB2 p.Ala167Thr Uncertain significance ★ ⚠ same type
CCNB2 p.Ala46Thr Uncertain significance ★ ⚠ same type
CCNB2 p.Arg196Gln 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/ccnb2-p-arg164cys (accessed [today's date]).

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