Is EGF p.Ala1037Val (c.3110C>T) pathogenic?

EGF p.Ala1037Val (c.3110C>T) is classified Uncertain significance in EGF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-07-16). AlphaMissense: likely benign (0.0978); Ultra-rare (popmax 0.0735%, eas); Associated with renal hypomagnesemia 4.

What condition is associated with EGF p.Ala1037Val (c.3110C>T)?

EGF p.Ala1037Val (c.3110C>T) is associated with renal hypomagnesemia 4 (ClinVar).

How common is EGF p.Ala1037Val (c.3110C>T) in the general population?

EGF p.Ala1037Val (c.3110C>T) is ultra-rare (popmax 0.0735%, eas) (gnomAD).

What do computational predictors say about EGF p.Ala1037Val (c.3110C>T)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

EGF p.Ala1037Val

c.3110C>T · rs572990451 · VCV347255

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0735%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

renal hypomagnesemia 4

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.438	indeterminate
SaProt	LLR -5.21	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.70 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.98	GERP 1.1, phastCons 0.45
Regional constraint	o/e 0.90	unconstrained · MANE · 68 kb · p 0.00042 · regional, not allelic
Overall
CADD	18.82	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 0.0735% East Asian · 33/44,874 alleles

Filtering AF 0.0538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.047%

Overall 0.00291% 47/1,614,064 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0735%	1,360
Remaining individualsnot grpmax-eligible	0.0144%	6,944
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00333%	30,009
African / African-American	0.00133%	75,026
European (non-Finnish)	8.47e-05%	1,180,027

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.Ala1037Val
Coding: c.3110C>T
MANE Select: NM_001963
dbSNP: rs572990451
Type: single nucleotide variant
Location: chr4:109999783 (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.Arg213Gln Uncertain significance ★★ ⚠ same condition
EGF p.Arg221Thr Uncertain significance ★★ ⚠ same condition
EGF p.Arg351Gln Uncertain significance ★★ ⚠ same condition
EGF p.Arg394Ter 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-ala1037val (accessed [today's date]).

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