Is ELF4 p.Lys236Glu (c.706A>G) pathogenic?

ELF4 p.Lys236Glu (c.706A>G) is classified Uncertain significance in ELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-19). AlphaMissense: likely pathogenic (0.917); Absent from gnomAD v4.1.

How common is ELF4 p.Lys236Glu (c.706A>G) in the general population?

ELF4 p.Lys236Glu (c.706A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELF4 p.Lys236Glu (c.706A>G)?

AlphaMissense predicts likely pathogenic (score 0.917) — an in-silico prediction, not a clinical call.

ELF4 p.Lys236Glu

c.706A>G · VCV3275128

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.917 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.917	likely pathogenic
REVEL	0.484	indeterminate
SaProt	LLR -10.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 1,701 bp · p 9e-08 · regional, not allelic
Overall
CADD	27.6	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: ELF4
Protein: p.Lys236Glu
Coding: c.706A>G
MANE Select: NM_001421
Type: single nucleotide variant
Location: chrX:130071143 (GRCh38)
Structure: AlphaFold pLDDT 49.77
Residue 236: a DNA-binding region

Full ELF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELF4 p.Gly206Asp Uncertain significance ★★ ⚠ same type
ELF4 p.Ser413Leu Uncertain significance ★★ ⚠ same type
ELF4 p.Ala147Val Benign/Likely benign ★★ same type
ELF4 p.Arg604Cys Benign ★★ same type
ELF4 p.Ser369= Benign ★★ same type
ELF4 p.Thr503= Benign ★★ same type
ELF4 p.Arg185Ter Likely pathogenic ★ same type
ELF4 p.Arg234Ter 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/elf4-p-lys236glu (accessed [today's date]).

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