Is ELF4 p.Trp251Ser (c.752G>C) pathogenic?

ELF4 p.Trp251Ser (c.752G>C) is classified Pathogenic in ELF4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-08). AlphaMissense: likely pathogenic (1); Absent from gnomAD v4.1; Associated with autoinflammatory syndrome, familial, X-linked, Behcet-like 2.

What condition is associated with ELF4 p.Trp251Ser (c.752G>C)?

ELF4 p.Trp251Ser (c.752G>C) is associated with autoinflammatory syndrome, familial, X-linked, Behcet-like 2 (ClinVar).

How common is ELF4 p.Trp251Ser (c.752G>C) in the general population?

ELF4 p.Trp251Ser (c.752G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELF4 p.Trp251Ser (c.752G>C)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

ELF4 p.Trp251Ser

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.752G>C · rs2124614205 · VCV1676293

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic ✓ concordant with ClinVar · top 3% in ELF4
REVEL	0.854	moderately pathogenic-leaning
SaProt	LLR -18.46	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 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	28.0	PHRED · no single calibrated threshold — expert panels disagree

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.Trp251Ser
Coding: c.752G>C
MANE Select: NM_001421
dbSNP: rs2124614205
Type: single nucleotide variant
Location: chrX:130071097 (GRCh38)
Structure: AlphaFold pLDDT 49.77
Residue 251: a DNA-binding region; a UniProt-annotated variant site (in aifbl2; elevated il17a expression in patient colon biopsies; patient cd8+ t cells have reduced prf1 expression when activated with il-2 compared to cd8+ t cells from a healthy donor; severely decreased transcriptional activity shown in ifnb1 promoter-driven luciferase assay)

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.Val242Met Uncertain significance ★ ⚠ same condition
ELF4 p.Trp231Arg 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-trp251ser (accessed [today's date]).

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