Is EGF p.Gly673Asp (c.2018G>A) pathogenic?

EGF p.Gly673Asp (c.2018G>A) is classified Uncertain significance in EGF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: likely pathogenic (0.8759); Very rare (popmax 0.00439%, sas).

How common is EGF p.Gly673Asp (c.2018G>A) in the general population?

EGF p.Gly673Asp (c.2018G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about EGF p.Gly673Asp (c.2018G>A)?

AlphaMissense predicts likely pathogenic (score 0.8759) — an in-silico prediction, not a clinical call.

EGF p.Gly673Asp

c.2018G>A · rs1253795861 · VCV2555139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8759 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8759	likely pathogenic · top 4% in EGF
REVEL	0.974	strongly pathogenic-leaning
SaProt	LLR -16.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 68 kb · p 0.00042 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00439% South Asian · 4/91,080 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000274% 4/1,461,772 alleles · very rare

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.Gly673Asp
Coding: c.2018G>A
MANE Select: NM_001963
dbSNP: rs1253795861
Type: single nucleotide variant
Location: chr4:109976200 (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

Similar variants

EGF c.2221+4C>T Uncertain significance ★★ same type
EGF c.2858-11G>T Uncertain significance ★★ same type
EGF c.-60C>T Uncertain significance ★★ same type
EGF p.Ala1025Ser Uncertain significance ★★ ⚠ same type
EGF p.Ala1037Val Uncertain significance ★★ ⚠ same type
EGF p.Ala45Val Uncertain significance ★★ ⚠ same type
EGF p.Ala862Thr Uncertain significance ★★ ⚠ same type
EGF p.Arg213Gln Uncertain significance ★★ ⚠ same type

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-gly673asp (accessed [today's date]).

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