Is CDKN1A p.Glu28Lys (c.82G>A) pathogenic?

CDKN1A p.Glu28Lys (c.82G>A) is classified Uncertain significance in CDKN1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.1332); Ultra-rare (popmax 0.012%, afr).

How common is CDKN1A p.Glu28Lys (c.82G>A) in the general population?

CDKN1A p.Glu28Lys (c.82G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about CDKN1A p.Glu28Lys (c.82G>A)?

AlphaMissense predicts likely benign (score 0.1332) — an in-silico prediction, not a clinical call.

CDKN1A p.Glu28Lys

c.82G>A · VCV4224733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1332 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1332	likely benign
REVEL	0.712	pathogenic-leaning
SaProt	LLR -9.73	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,695 bp · p 0.06 · regional, not allelic
Overall
CADD	26.6	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 0.012% African / African-American · 9/75,068 alleles

Filtering AF 0.00622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.000806% 13/1,611,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,341
Finnishnot grpmax-eligible	0.00162%	61,868
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.000169%	589,995

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: CDKN1A
Protein: p.Glu28Lys
Coding: c.82G>A
MANE Select: NM_000389
Type: single nucleotide variant
Location: chr6:36684183 (GRCh38)
Gene constraint: LOEUF 1.492 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.16 · 13 PDB
Residue 28: an α-helix

Full CDKN1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKN1A p.Arg84Gln Likely benign ★★ ⚠ same type
CDKN1A p.Pro4= Benign/Likely benign ★★ same type
CDKN1A p.Ser31= Likely benign ★★ same type
CDKN1A p.Thr80= Likely benign ★★ same type
CDKN1A p.Ala106Val Uncertain significance ★ ⚠ same type
CDKN1A p.Arg20His Uncertain significance ★ ⚠ same type
CDKN1A p.Arg32His Uncertain significance ★ ⚠ same type
CDKN1A p.Arg46His 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/cdkn1a-p-glu28lys (accessed [today's date]).

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