Is CDK11A p.Cys57Ser (c.170G>C) pathogenic?

CDK11A p.Cys57Ser (c.170G>C) is classified Uncertain significance in CDK11A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.2431); Very rare (popmax 0.0067%, eas).

How common is CDK11A p.Cys57Ser (c.170G>C) in the general population?

CDK11A p.Cys57Ser (c.170G>C) is very rare (popmax 0.0067%, eas) (gnomAD).

What do computational predictors say about CDK11A p.Cys57Ser (c.170G>C)?

AlphaMissense predicts likely benign (score 0.2431) — an in-silico prediction, not a clinical call.

CDK11A p.Cys57Ser

c.170G>C · VCV4651304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2431 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2431	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -1.86	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 0.27	phastCons 0.99
Regional constraint	o/e 1.02	unconstrained · MANE · 5,337 bp · p 0.77 · regional, not allelic
Overall
CADD	20.9	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 0.0067% East Asian · 3/44,788 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000187% 3/1,603,584 alleles · very rare exomes 2/1,452,488 · genomes 1/151,096 · joint denominator

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: CDK11A
Protein: p.Cys57Ser
Coding: c.170G>C
MANE Select: NM_024011
Type: single nucleotide variant
Location: chr1:1721653 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.94
Residue 57: the 'disordered' region; a UniProt-annotated variant site (in)

Full CDK11A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK11A p.Arg247Gln Uncertain significance ★★ ⚠ same type
CDK11A p.Ala196Val Uncertain significance ★ ⚠ same type
CDK11A p.Ala558Thr Uncertain significance ★ ⚠ same type
CDK11A p.Ala590Thr Uncertain significance ★ same type
CDK11A p.Ala597Val Uncertain significance ★ ⚠ same type
CDK11A p.Arg131Cys Uncertain significance ★ ⚠ same type
CDK11A p.Arg132Gln Uncertain significance ★ ⚠ same type
CDK11A p.Arg132Trp 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/cdk11a-p-cys57ser (accessed [today's date]).

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