Is CDK4 p.Arg210Gln (c.629G>A) pathogenic?

CDK4 p.Arg210Gln (c.629G>A) is classified Conflicting classifications of pathogenicity in CDK4 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.2546); Very rare (popmax 0.0055%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with CDK4 p.Arg210Gln (c.629G>A)?

CDK4 p.Arg210Gln (c.629G>A) is associated with hereditary neoplastic syndrome, familial melanoma (ClinVar).

How common is CDK4 p.Arg210Gln (c.629G>A) in the general population?

CDK4 p.Arg210Gln (c.629G>A) is very rare (popmax 0.0055%, sas) (gnomAD).

What do computational predictors say about CDK4 p.Arg210Gln (c.629G>A)?

AlphaMissense predicts likely benign (score 0.2546) — an in-silico prediction, not a clinical call.

CDK4 p.Arg210Gln

c.629G>A · rs373619077 · VCV463473

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0055%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2546	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -8.78	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 2, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 3,189 bp · p 2e-07 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0055% South Asian · 5/90,958 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00118% 19/1,609,128 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0055%	18,192
African / African-American	0.00133%	74,946
European (non-Finnish)	0.00111%	90,415

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: CDK4
Protein: p.Arg210Gln
Coding: c.629G>A
MANE Select: NM_000075
dbSNP: rs373619077
Type: single nucleotide variant
Location: chr12:57750659 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.57 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 15 PDB
Residue 210: the protein kinase domain

Full CDK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial melanoma

Similar variants

CDK4 p.Arg210= Benign/Likely benign ★★ same residue
CDK4 p.Arg210Leu Uncertain significance ★ ⚠ same residue
CDK4 p.Arg210Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
CDK4 p.Arg210Ter Conflicting classifications of pathogenicity ★ same residue
CDK4 p.Arg24Cys Pathogenic ★★ same condition
CDK4 p.Arg24His Pathogenic ★★ same condition
CDK4 c.354+3G>C Uncertain significance ★★ same condition
CDK4 c.354+5G>T Uncertain significance ★★ same condition

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/cdk4-p-arg210gln (accessed [today's date]).

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