Is ELF4 p.Val411Met (c.1231G>A) pathogenic?

ELF4 p.Val411Met (c.1231G>A) is classified Likely benign in ELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-10). AlphaMissense: likely benign (0.0834); Rare (popmax 0.384%, afr).

How common is ELF4 p.Val411Met (c.1231G>A) in the general population?

ELF4 p.Val411Met (c.1231G>A) is rare (popmax 0.384%, afr) (gnomAD).

What do computational predictors say about ELF4 p.Val411Met (c.1231G>A)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

ELF4 p.Val411Met

c.1231G>A · VCV4847946

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.384%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.96	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 0.075	GERP 0.43
Regional constraint	o/e 0.97	unconstrained · MANE · 2,786 bp · p 0.57 · regional, not allelic
Overall
CADD	2.674	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 0.384% African / African-American · 220/57,277 alleles

Filtering AF 0.342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.326%

Overall 0.0259% 313/1,210,172 alleles · rare exomes 204/1,098,091 · genomes 109/112,081 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.384%	260
Ashkenazi Jewishnot grpmax-eligible	0.191%	525
Remaining individualsnot grpmax-eligible	0.0252%	3,968
Middle Eastern	0.023%	4,352
Admixed American	0.00654%	15,285
South Asian	0.00528%	18,946
European (non-Finnish)	0.00357%	27,973

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.Val411Met
Coding: c.1231G>A
MANE Select: NM_001421
Type: single nucleotide variant
Location: chrX:130067482 (GRCh38)
Structure: AlphaFold pLDDT 49.77
Residue 411: 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-val411met (accessed [today's date]).

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