Is ELF3 p.Glu290Lys (c.868G>A) pathogenic?

ELF3 p.Glu290Lys (c.868G>A) is classified Uncertain significance in ELF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). AlphaMissense: likely benign (0.1651); Very rare (popmax 0.00446%, eas).

How common is ELF3 p.Glu290Lys (c.868G>A) in the general population?

ELF3 p.Glu290Lys (c.868G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about ELF3 p.Glu290Lys (c.868G>A)?

AlphaMissense predicts likely benign (score 0.1651) — an in-silico prediction, not a clinical call.

ELF3 p.Glu290Lys

c.868G>A · rs149307595 · VCV2519797

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1651	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -5.56	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 5	GERP -1.2, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 1,440 bp · p 3.5e-07 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00446% East Asian · 2/44,874 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000558% 9/1,614,102 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,437
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000424%	235,997

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: ELF3
Protein: p.Glu290Lys
Coding: c.868G>A
MANE Select: NM_004433
dbSNP: rs149307595
Type: single nucleotide variant
Location: chr1:202013891 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.32 · 1 PDB
Residue 290: a DNA-binding region

Full ELF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELF3 p.Asn104= Benign ★★ same type
ELF3 p.Arg205Trp Uncertain significance ★ ⚠ same type
ELF3 p.Arg233Cys Uncertain significance ★ ⚠ same type
ELF3 p.Arg307His Uncertain significance ★ ⚠ same type
ELF3 p.Arg370Gln Uncertain significance ★ ⚠ same type
ELF3 p.Arg370Trp Uncertain significance ★ ⚠ same type
ELF3 p.Asp220Tyr Uncertain significance ★ ⚠ same type
ELF3 p.Asp234Asn Uncertain significance ★ ⚠ 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/elf3-p-glu290lys (accessed [today's date]).

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