Is EGF p.Glu793Val (c.2378A>T) pathogenic?

EGF p.Glu793Val (c.2378A>T) is classified Uncertain significance in EGF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-08). AlphaMissense: likely benign (0.1281); Ultra-rare (popmax 0.0991%, mid); Associated with renal hypomagnesemia 4.

What condition is associated with EGF p.Glu793Val (c.2378A>T)?

EGF p.Glu793Val (c.2378A>T) is associated with renal hypomagnesemia 4 (ClinVar).

How common is EGF p.Glu793Val (c.2378A>T) in the general population?

EGF p.Glu793Val (c.2378A>T) is ultra-rare (popmax 0.0991%, mid) (gnomAD).

What do computational predictors say about EGF p.Glu793Val (c.2378A>T)?

AlphaMissense predicts likely benign (score 0.1281) — an in-silico prediction, not a clinical call.

EGF p.Glu793Val

c.2378A>T · rs369597497 · VCV1410240

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1281 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0991%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal hypomagnesemia 4

Computational evidence

Protein change
AlphaMissense	0.1281	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -6.56	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 1.6	GERP -2.7, phastCons 0.001
Regional constraint	o/e 0.90	unconstrained · MANE · 68 kb · p 0.00042 · regional, not allelic
Overall
CADD	13.26	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 0.0991% Middle Eastern · 6/6,056 alleles

Filtering AF 0.043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0295%

Overall 0.00824% 133/1,613,598 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0991%	1,009
Admixed American	0.0217%	4,614
Remaining individualsnot grpmax-eligible	0.0208%	4,806
European (non-Finnish)	0.00831%	12,038
African / African-American	0.00266%	37,526
South Asian	0.0011%	91,050

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.Glu793Val
Coding: c.2378A>T
MANE Select: NM_001963
dbSNP: rs369597497
Type: single nucleotide variant
Location: chr4:109983428 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.66 · 13 PDB

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-glu793val (accessed [today's date]).

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