Is EGF p.Glu920= (c.2760G>A) pathogenic?

EGF p.Glu920= (c.2760G>A) is classified Conflicting classifications of pathogenicity in EGF (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2018-08-01). Ultra-rare (popmax 0.03%, amr); Associated with renal hypomagnesemia 4.

What condition is associated with EGF p.Glu920= (c.2760G>A)?

EGF p.Glu920= (c.2760G>A) is associated with renal hypomagnesemia 4 (ClinVar).

How common is EGF p.Glu920= (c.2760G>A) in the general population?

EGF p.Glu920= (c.2760G>A) is ultra-rare (popmax 0.03%, amr) (gnomAD).

EGF p.Glu920=

c.2760G>A · rs760507781 · VCV762429

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Conditions

renal hypomagnesemia 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -4.4
Overall
CADD	0.726	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/59,990 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.0151% 244/1,613,682 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.223%	448
Admixed Americangrpmax	0.03%	3,333
Remaining individualsnot grpmax-eligible	0.0224%	4,462
European (non-Finnish)	0.0121%	8,251
South Asian	0.00329%	30,356

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EGF
Protein: p.Glu920=
Coding: c.2760G>A
MANE Select: NM_001963
dbSNP: rs760507781
Type: single nucleotide variant
Location: chr4:109993272 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.66 · 13 PDB
Residue 920: the egf-like 8; calcium-binding domain; a disulfide bond; a UniProt-annotated variant site (in)

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

Disease context

renal hypomagnesemia 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EGF c.2221+4C>T Uncertain significance ★★ same condition
EGF c.2858-11G>T Uncertain significance ★★ same condition
EGF c.-60C>T Uncertain significance ★★ same condition
EGF p.Ala1025Ser Uncertain significance ★★ ⚠ same condition
EGF p.Ala1037Val Uncertain significance ★★ ⚠ same condition
EGF p.Arg213Gln Uncertain significance ★★ ⚠ same condition
EGF p.Arg221Thr Uncertain significance ★★ ⚠ same condition
EGF p.Arg351Gln Uncertain significance ★★ ⚠ same condition

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/egf-p-glu920 (accessed [today's date]).

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