Is ELF4 p.Ala95Thr (c.283G>A) pathogenic?

ELF4 p.Ala95Thr (c.283G>A) is classified Likely benign in ELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). AlphaMissense: likely benign (0.0618); Rare (popmax 0.551%, mid).

How common is ELF4 p.Ala95Thr (c.283G>A) in the general population?

ELF4 p.Ala95Thr (c.283G>A) is rare (popmax 0.551%, mid) (gnomAD).

What do computational predictors say about ELF4 p.Ala95Thr (c.283G>A)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

ELF4 p.Ala95Thr

c.283G>A · VCV4533901

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.551%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -0.53, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 2,893 bp · p 0.65 · regional, not allelic
Overall
CADD	1.282	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 0.551% Middle Eastern · 24/4,355 alleles

Filtering AF 0.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.323%

Overall 0.0226% 273/1,209,873 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.551%	181
Admixed American	0.101%	994
Remaining individualsnot grpmax-eligible	0.0231%	4,328
European (non-Finnish)	0.0213%	4,687
African / African-American	0.00175%	57,113

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.Ala95Thr
Coding: c.283G>A
MANE Select: NM_001421
Type: single nucleotide variant
Location: chrX:130074106 (GRCh38)
Structure: AlphaFold pLDDT 49.77
Residue 95: a UniProt-annotated variant site (no effect on transcriptional activity shown in ifnb1 promoter-driven luciferase assay); the 'runx1-binding' region

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

Similar variants

ELF4 p.Ala95= Likely benign ★ same residue
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

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-ala95thr (accessed [today's date]).

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