Is EGF p.Pro607= (c.1821A>G) pathogenic?

EGF p.Pro607= (c.1821A>G) is classified Conflicting classifications of pathogenicity in EGF (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-19). Rare (popmax 0.109%, eas); Associated with renal hypomagnesemia 4.

What condition is associated with EGF p.Pro607= (c.1821A>G)?

EGF p.Pro607= (c.1821A>G) is associated with renal hypomagnesemia 4 (ClinVar).

How common is EGF p.Pro607= (c.1821A>G) in the general population?

EGF p.Pro607= (c.1821A>G) is rare (popmax 0.109%, eas) (gnomAD).

EGF p.Pro607=

c.1821A>G · rs200400376 · VCV900057

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.109%, eas)

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 -0.12	GERP -3.9
Overall
CADD	6.262	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% East Asian · 49/44,832 alleles

Filtering AF 0.0849% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0762%

Overall 0.00744% 120/1,612,682 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.109%	915
Remaining individualsnot grpmax-eligible	0.0672%	1,487
African / African-American	0.00933%	10,718
Admixed American	0.005%	20,002
European (non-Finnish)	0.00153%	65,489
South Asian	0.0011%	91,064

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.Pro607=
Coding: c.1821A>G
MANE Select: NM_001963
dbSNP: rs200400376
Type: single nucleotide variant
Location: chr4:109974799 (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-pro607 (accessed [today's date]).

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