Is CDK7 p.Arg11Leu (c.32G>T) pathogenic?

CDK7 p.Arg11Leu (c.32G>T) is classified Uncertain significance in CDK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). AlphaMissense: likely pathogenic (0.8499); Ultra-rare (popmax 0.0107%, afr).

How common is CDK7 p.Arg11Leu (c.32G>T) in the general population?

CDK7 p.Arg11Leu (c.32G>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about CDK7 p.Arg11Leu (c.32G>T)?

AlphaMissense predicts likely pathogenic (score 0.8499) — an in-silico prediction, not a clinical call.

CDK7 p.Arg11Leu

c.32G>T · VCV3830913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8499 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8499	likely pathogenic
REVEL	0.257	benign-leaning
SaProt	LLR -8.75	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 42 kb · p 2.4e-06 · regional, not allelic
Overall
CADD	27.2	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 0.0107% African / African-American · 8/74,894 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000499% 8/1,603,574 alleles · ultra-rare

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: CDK7
Protein: p.Arg11Leu
Coding: c.32G>T
MANE Select: NM_001799
Type: single nucleotide variant
Location: chr5:69235007 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI 0.31 (gnomAD)
Structure: AlphaFold pLDDT 82.29 · 56 PDB

Full CDK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK7 p.Arg11Ser Uncertain significance ★ ⚠ same residue
CDK7 p.Ala180Thr Uncertain significance ★ ⚠ same type
CDK7 p.Asn35Tyr Uncertain significance ★ ⚠ same type
CDK7 p.Asn86Asp Uncertain significance ★ ⚠ same type
CDK7 p.Asp104Gly Uncertain significance ★ ⚠ same type
CDK7 p.Asp146Glu Uncertain significance ★ ⚠ same type
CDK7 p.Asp267Asn Uncertain significance ★ ⚠ same type
CDK7 p.Leu145Val 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/cdk7-p-arg11leu (accessed [today's date]).

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