Is CDK6 p.Pro148= (c.444A>T) pathogenic?

CDK6 p.Pro148= (c.444A>T) is classified Benign in CDK6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-01). Low-frequency (popmax 1.34%, nfe).

How common is CDK6 p.Pro148= (c.444A>T) in the general population?

CDK6 p.Pro148= (c.444A>T) is low-frequency (popmax 1.34%, nfe) (gnomAD).

CDK6 p.Pro148=

c.444A>T · rs34257565 · VCV769332

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.34%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.4	GERP -4.2, phastCons 0.2
Overall
CADD	8.159	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.34% European (non-Finnish) · 15,852/1,179,942 alleles

Filtering AF 1.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.32%

Overall 1.12% 18,089/1,614,074 alleles · low-frequency exomes 16,669/1,461,756 · genomes 1,420/152,318 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.29%	30
Ashkenazi Jewishnot grpmax-eligible	1.48%	68
European (non-Finnish)grpmax	1.34%	74
Remaining individualsnot grpmax-eligible	0.989%	101
Admixed American	0.908%	110
Finnishnot grpmax-eligible	0.523%	191
Middle Eastern	0.248%	404
African / African-American	0.24%	417
South Asian	0.0802%	1,248
East Asian	0.00669%	14,958

Amish 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: CDK6
Protein: p.Pro148=
Coding: c.444A>T
MANE Select: NM_001145306
dbSNP: rs34257565
Type: single nucleotide variant
Location: chr7:92725719 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.81 · 22 PDB
Residue 148: the protein kinase domain; an α-helix

Full CDK6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK6 c.370-118G>A Benign ★★ same type
CDK6 c.537+257A>T Benign ★★ same type
CDK6 c.538-14G>A Benign ★★ same type
CDK6 c.647+153C>T Benign ★★ same type
CDK6 c.698+147G>C Benign ★★ same type
CDK6 c.699-18T>C Benign ★★ same type
CDK6 c.834+53T>C Benign ★★ same type
CDK6 c.*32G>A Benign ★★ 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/cdk6-p-pro148 (accessed [today's date]).

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