Is ELF4 p.Val242Met (c.724G>A) pathogenic?

ELF4 p.Val242Met (c.724G>A) is classified Uncertain significance in ELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-28). AlphaMissense: likely pathogenic (0.9883); Absent from gnomAD v4.1; Associated with autoinflammatory syndrome, familial, X-linked, Behcet-like 2.

What condition is associated with ELF4 p.Val242Met (c.724G>A)?

ELF4 p.Val242Met (c.724G>A) is associated with autoinflammatory syndrome, familial, X-linked, Behcet-like 2 (ClinVar).

How common is ELF4 p.Val242Met (c.724G>A) in the general population?

ELF4 p.Val242Met (c.724G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELF4 p.Val242Met (c.724G>A)?

AlphaMissense predicts likely pathogenic (score 0.9883) — an in-silico prediction, not a clinical call.

ELF4 p.Val242Met

Q: How is X-linked immune dysregulation with inflammatory bowel disease due to ELF4 deficiency inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.724G>A · rs2523027297 · VCV2441684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9883 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autoinflammatory syndrome, familial, X-linked, Behcet-like 2

Computational evidence

Protein change
AlphaMissense	0.9883	likely pathogenic · top 8% in ELF4
REVEL	0.462	indeterminate
SaProt	LLR -13.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 1,701 bp · p 9e-08 · regional, not allelic
Overall
CADD	27.5	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.Val242Met
Coding: c.724G>A
MANE Select: NM_001421
dbSNP: rs2523027297
Type: single nucleotide variant
Location: chrX:130071125 (GRCh38)
Structure: AlphaFold pLDDT 49.77
Residue 242: a DNA-binding region

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

Disease context

autoinflammatory syndrome, familial, X-linked, Behcet-like 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked immune dysregulation with inflammatory bowel disease due to ELF4 deficiency (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy

Similar variants

ELF4 p.Gly206Asp Uncertain significance ★★ ⚠ same condition
ELF4 p.Asn223Ile Uncertain significance ★ ⚠ same condition
ELF4 p.Gly237Ala Uncertain significance ★ ⚠ same condition
ELF4 p.Gly237Val Uncertain significance ★ ⚠ same condition
ELF4 p.Lys280Glu Uncertain significance ★ same condition
ELF4 p.Pro646Ser Uncertain significance ★ ⚠ same condition
ELF4 p.Trp231Arg Pathogenic same condition
ELF4 p.Trp251Ser Pathogenic 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/elf4-p-val242met (accessed [today's date]).

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