Is KDM5B p.Phe700Val (c.2098T>G) pathogenic?

KDM5B p.Phe700Val (c.2098T>G) is classified Uncertain significance in KDM5B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-27). AlphaMissense: likely pathogenic (0.9163); Absent from gnomAD v4.1.

How common is KDM5B p.Phe700Val (c.2098T>G) in the general population?

KDM5B p.Phe700Val (c.2098T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDM5B p.Phe700Val (c.2098T>G)?

AlphaMissense predicts likely pathogenic (score 0.9163) — an in-silico prediction, not a clinical call.

KDM5B p.Phe700Val

c.2098T>G · rs1655553669 · VCV1712901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9163 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9163	likely pathogenic
REVEL	0.806	moderately pathogenic-leaning
SaProt	LLR -10.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 27 kb · p 0.42 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Phe700Val
Coding: c.2098T>G
MANE Select: NM_006618
dbSNP: rs1655553669
Type: single nucleotide variant
Location: chr1:202746242 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.52 · 56 PDB
Residue 700: a UniProt-annotated variant site (in mrt65)

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

Similar variants

KDM5B c.2945+1G>A Likely pathogenic ★★ same type
KDM5B p.Arg1047Ter Pathogenic/Likely pathogenic ★★ same type
KDM5B p.Arg1214Ter Likely pathogenic ★★ same type
KDM5B p.Arg1253Ter Pathogenic/Likely pathogenic ★★ same type
KDM5B p.Arg1281Ter Pathogenic/Likely pathogenic ★★ same type
KDM5B p.Arg1426Ter Pathogenic/Likely pathogenic ★★ same type
KDM5B p.Arg259Ter Pathogenic/Likely pathogenic ★★ same type
KDM5B p.Arg299Ter Pathogenic/Likely pathogenic ★★ 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/kdm5b-p-phe700val (accessed [today's date]).

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