Is KDM5B p.Pro20Ala (c.58C>G) pathogenic?

KDM5B p.Pro20Ala (c.58C>G) is classified Uncertain significance in KDM5B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-01). AlphaMissense: likely benign (0.0562); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KDM5B p.Pro20Ala (c.58C>G)?

KDM5B p.Pro20Ala (c.58C>G) is associated with Inborn genetic diseases (ClinVar).

How common is KDM5B p.Pro20Ala (c.58C>G) in the general population?

KDM5B p.Pro20Ala (c.58C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM5B p.Pro20Ala (c.58C>G)?

AlphaMissense predicts likely benign (score 0.0562) — an in-silico prediction, not a clinical call.

KDM5B p.Pro20Ala

c.58C>G · rs2527803096 · VCV2615033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0562 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0562	likely benign
REVEL	0.232	benign-leaning
SaProt	LLR -6.17	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 9	GERP -1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 46 kb · p 0.3 · regional, not allelic
Overall
CADD	22.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KDM5B
Protein: p.Pro20Ala
Coding: c.58C>G
MANE Select: NM_006618
dbSNP: rs2527803096
Type: single nucleotide variant
Location: chr1:202808248 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.52 · 56 PDB

Full KDM5B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KDM5B p.Ala747Thr Uncertain significance ★★ ⚠ same condition
KDM5B p.Arg619His Uncertain significance ★★ ⚠ same condition
KDM5B p.Arg733Trp Uncertain significance ★★ ⚠ same condition
KDM5B p.Arg827Gln Uncertain significance ★★ ⚠ same condition
KDM5B p.Arg843Gln Uncertain significance ★★ ⚠ same condition
KDM5B p.Arg843Trp Uncertain significance ★★ ⚠ same condition
KDM5B p.Asn1347Ser Uncertain significance ★★ ⚠ same condition
KDM5B p.Asp1498Glu 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/kdm5b-p-pro20ala (accessed [today's date]).

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