Is EGF p.Val1033= (c.3099C>T) pathogenic?

EGF p.Val1033= (c.3099C>T) is classified Likely benign in EGF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-09-30). Ultra-rare (popmax 0.0222%, nfe); Associated with renal hypomagnesemia 4.

What condition is associated with EGF p.Val1033= (c.3099C>T)?

EGF p.Val1033= (c.3099C>T) is associated with renal hypomagnesemia 4 (ClinVar).

How common is EGF p.Val1033= (c.3099C>T) in the general population?

EGF p.Val1033= (c.3099C>T) is ultra-rare (popmax 0.0222%, nfe) (gnomAD).

EGF p.Val1033=

c.3099C>T · rs144628857 · VCV740956

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0222%, nfe)

Conditions

renal hypomagnesemia 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.95 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.14	GERP 0.85
Overall
CADD	6.203	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0222% European (non-Finnish) · 262/1,180,032 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0191%

Overall 0.0164% 265/1,613,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0222%	4,504
Remaining individualsnot grpmax-eligible	0.0032%	31,242
African / African-American	0.00134%	74,882

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.Val1033=
Coding: c.3099C>T
MANE Select: NM_001963
dbSNP: rs144628857
Type: single nucleotide variant
Location: chr4:109999772 (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-val1033 (accessed [today's date]).

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