Is EDF1 p.Asp5Gly (c.14A>G) pathogenic?

EDF1 p.Asp5Gly (c.14A>G) is classified Uncertain significance in EDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: likely pathogenic (0.7578); Very rare (popmax 0.00417%, nfe).

How common is EDF1 p.Asp5Gly (c.14A>G) in the general population?

EDF1 p.Asp5Gly (c.14A>G) is very rare (popmax 0.00417%, nfe) (gnomAD).

What do computational predictors say about EDF1 p.Asp5Gly (c.14A>G)?

AlphaMissense predicts likely pathogenic (score 0.7578) — an in-silico prediction, not a clinical call.

EDF1 p.Asp5Gly

c.14A>G · VCV3506679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7578 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00417%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7578	likely pathogenic
REVEL	0.251	benign-leaning
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,971 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00417% European (non-Finnish) · 49/1,175,440 alleles

Filtering AF 0.00319% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00287%

Overall 0.00312% 50/1,600,128 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00417%	23,989
Remaining individualsnot grpmax-eligible	0.00161%	62,024

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: EDF1
Protein: p.Asp5Gly
Coding: c.14A>G
MANE Select: NM_003792
Type: single nucleotide variant
Location: chr9:136866245 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 83.47 · 7 PDB

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.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
EDF1 p.Ser4Arg 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-asp5gly (accessed [today's date]).

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