Is ELF3 p.Arg307His (c.920G>A) pathogenic?

ELF3 p.Arg307His (c.920G>A) is classified Uncertain significance in ELF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: ambiguous (0.5271); Very rare (popmax 0.00667%, amr).

How common is ELF3 p.Arg307His (c.920G>A) in the general population?

ELF3 p.Arg307His (c.920G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about ELF3 p.Arg307His (c.920G>A)?

AlphaMissense predicts ambiguous (score 0.5271) — an in-silico prediction, not a clinical call.

ELF3 p.Arg307His

c.920G>A · VCV4017474

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5271 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5271	ambiguous
REVEL	0.284	benign-leaning
SaProt	LLR -9.52	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP -1.1, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 1,440 bp · p 3.5e-07 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00667% Admixed American · 4/59,976 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.0044% 71/1,613,876 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,994
European (non-Finnish)	0.00542%	18,437
Remaining individualsnot grpmax-eligible	0.0032%	31,239
African / African-American	0.00133%	74,914

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.Arg307His
Coding: c.920G>A
MANE Select: NM_004433
Type: single nucleotide variant
Location: chr1:202013943 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.32 · 1 PDB
Residue 307: 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.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
ELF3 p.Asp96Glu 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-arg307his (accessed [today's date]).

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