Is KDM4E p.Val471Phe (c.1411G>T) pathogenic?

KDM4E p.Val471Phe (c.1411G>T) is classified Uncertain significance in KDM4E (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-19). AlphaMissense: likely benign (0.0741); Rare (popmax 0.838%, nfe).

How common is KDM4E p.Val471Phe (c.1411G>T) in the general population?

KDM4E p.Val471Phe (c.1411G>T) is rare (popmax 0.838%, nfe) (gnomAD).

What do computational predictors say about KDM4E p.Val471Phe (c.1411G>T)?

AlphaMissense predicts likely benign (score 0.0741) — an in-silico prediction, not a clinical call.

KDM4E p.Val471Phe

c.1411G>T · VCV4091310

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0741 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.838%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0741	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -8.08	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 -5.5	GERP -3
Regional constraint	o/e 1.03	unconstrained · MANE · 839 bp · p 0.58 · regional, not allelic
Overall
CADD	0.035	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 0.838% European (non-Finnish) · 9,615/1,146,912 alleles

Filtering AF 0.824% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.819%

Overall 0.682% 10,483/1,537,244 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.838%	119
Remaining individualsnot grpmax-eligible	0.651%	154
Finnishnot grpmax-eligible	0.502%	199
African / African-American	0.122%	822
South Asian	0.113%	885
Amishnot grpmax-eligible	0.11%	912
Ashkenazi Jewishnot grpmax-eligible	0.108%	924
Admixed American	0.0549%	1,821
Middle Eastern	0.0501%	1,997
East Asian	0.00244%	40,910

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: KDM4E
Protein: p.Val471Phe
Coding: c.1411G>T
MANE Select: NM_001161630
Type: single nucleotide variant
Location: chr11:95026968 (GRCh38)
Structure: AlphaFold pLDDT 76.85 · 1 PDB
Residue 471: the 'disordered' region

Full KDM4E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KDM4E p.Val471Ala Uncertain significance ★ ⚠ same residue
KDM4E p.Ala187= Likely benign ★★ same type
KDM4E p.Cys381Tyr Benign ★★ same type
KDM4E p.Gln42Arg Benign ★★ same type
KDM4E p.Thr190= Likely benign ★★ same type
KDM4E p.Ala224Asp Uncertain significance ★ ⚠ same type
KDM4E p.Ala265Val Uncertain significance ★ ⚠ same type
KDM4E p.Ala287Thr 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/kdm4e-p-val471phe (accessed [today's date]).

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