Is ELF4 p.Val382Ile (c.1144G>A) pathogenic?

ELF4 p.Val382Ile (c.1144G>A) is classified Likely benign in ELF4 (ClinVar, Single submitter, 3 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.076); Rare (popmax 0.459%, mid).

How common is ELF4 p.Val382Ile (c.1144G>A) in the general population?

ELF4 p.Val382Ile (c.1144G>A) is rare (popmax 0.459%, mid) (gnomAD).

What do computational predictors say about ELF4 p.Val382Ile (c.1144G>A)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

ELF4 p.Val382Ile

c.1144G>A · rs148953158 · VCV1328021

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.459%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.41	GERP -0.86, phastCons 0.67
Regional constraint	o/e 0.97	unconstrained · MANE · 2,786 bp · p 0.57 · regional, not allelic
Overall
CADD	11.09	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

Grpmax group 0.459% Middle Eastern · 20/4,357 alleles

Filtering AF 0.304% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.254%

Overall 0.019% 230/1,210,842 alleles · rare exomes 211/1,098,228 · genomes 19/112,614 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.459%	218
South Asian	0.072%	1,388
Remaining individualsnot grpmax-eligible	0.0336%	2,975
Ashkenazi Jewishnot grpmax-eligible	0.0318%	3,149
African / African-American	0.0313%	3,192
European (non-Finnish)	0.0136%	7,340
Admixed American	0.0131%	7,647

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: ELF4
Protein: p.Val382Ile
Coding: c.1144G>A
MANE Select: NM_001421
dbSNP: rs148953158
Type: single nucleotide variant
Location: chrX:130069343 (GRCh38)
Structure: AlphaFold pLDDT 49.77
Residue 382: a UniProt-annotated variant site (no effect on transcriptional activity shown in ifnb1 promoter-driven luciferase assay)

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-val382ile (accessed [today's date]).

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