Is EGF p.Thr779= (c.2337G>A) pathogenic?

EGF p.Thr779= (c.2337G>A) is classified Conflicting classifications of pathogenicity in EGF (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-08-30). Ultra-rare (popmax 0.0351%, sas); Associated with renal hypomagnesemia 4.

What condition is associated with EGF p.Thr779= (c.2337G>A)?

EGF p.Thr779= (c.2337G>A) is associated with renal hypomagnesemia 4 (ClinVar).

How common is EGF p.Thr779= (c.2337G>A) in the general population?

EGF p.Thr779= (c.2337G>A) is ultra-rare (popmax 0.0351%, sas) (gnomAD).

EGF p.Thr779=

c.2337G>A · rs368323208 · VCV901215

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0351%, sas)

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 1.3	GERP -0.81, phastCons 0.81
Overall
CADD	9.387	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0351% South Asian · 32/91,088 alleles

Filtering AF 0.0256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.0103% 166/1,613,978 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0351%	2,846
European (non-Finnish)	0.011%	9,077
Admixed American	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00156%	64,030
African / African-American	0.00134%	74,902

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.Thr779=
Coding: c.2337G>A
MANE Select: NM_001963
dbSNP: rs368323208
Type: single nucleotide variant
Location: chr4:109980941 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.66 · 13 PDB
Residue 779: the egf-like 5 domain; a disulfide bond

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 p.Thr779Met Uncertain significance ★ ⚠ same residue
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

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-thr779 (accessed [today's date]).

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