Is EDF1 p.Val73Met (c.217G>A) pathogenic?

EDF1 p.Val73Met (c.217G>A) is classified Uncertain significance in EDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). AlphaMissense: likely pathogenic (0.8067); Absent from gnomAD v4.1.

How common is EDF1 p.Val73Met (c.217G>A) in the general population?

EDF1 p.Val73Met (c.217G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDF1 p.Val73Met (c.217G>A)?

AlphaMissense predicts likely pathogenic (score 0.8067) — an in-silico prediction, not a clinical call.

EDF1 p.Val73Met

c.217G>A · VCV3506682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8067 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8067	likely pathogenic
REVEL	0.426	indeterminate
SaProt	LLR -12.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.58, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,971 bp · p 1.5e-05 · 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EDF1
Protein: p.Val73Met
Coding: c.217G>A
MANE Select: NM_003792
Type: single nucleotide variant
Location: chr9:136863362 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 83.47 · 7 PDB
Residue 73: the 'interaction with nr5a2, pparg and nr1h3' region; the 'interaction with tbp and nr5a1' region

Full EDF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDF1 p.Ala147Val Uncertain significance ★ ⚠ same type
EDF1 p.Arg126Trp Uncertain significance ★ ⚠ same type
EDF1 p.Arg133Gln Uncertain significance ★ ⚠ same type
EDF1 p.Asp5Gly Uncertain significance ★ ⚠ same type
EDF1 p.Gln92Arg Uncertain significance ★ ⚠ same type
EDF1 p.Ile137Val Uncertain significance ★ ⚠ same type
EDF1 p.Lys135Glu Uncertain significance ★ ⚠ same type
EDF1 p.Lys15Gln 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/edf1-p-val73met (accessed [today's date]).

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