Is EED p.Ile44Val (c.130A>G) pathogenic?

EED p.Ile44Val (c.130A>G) is classified Uncertain significance in EED (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: likely benign (0.0547); Ultra-rare (popmax 0.0151%, sas); Associated with Inborn genetic diseases.

What condition is associated with EED p.Ile44Val (c.130A>G)?

EED p.Ile44Val (c.130A>G) is associated with Inborn genetic diseases (ClinVar).

How common is EED p.Ile44Val (c.130A>G) in the general population?

EED p.Ile44Val (c.130A>G) is ultra-rare (popmax 0.0151%, sas) (gnomAD).

What do computational predictors say about EED p.Ile44Val (c.130A>G)?

AlphaMissense predicts likely benign (score 0.0547) — an in-silico prediction, not a clinical call.

EED p.Ile44Val

c.130A>G · rs749513327 · VCV2403367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0547 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0151%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0547	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -5.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 0.94, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 5,145 bp · p 0.013 · regional, not allelic
Overall
CADD	18.43	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 0.0151% South Asian · 13/86,350 alleles

Filtering AF 0.00888% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00705%

Overall 0.00183% 29/1,582,624 alleles · ultra-rare exomes 26/1,430,406 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0151%	6,642
Admixed American	0.00188%	53,186
Remaining individualsnot grpmax-eligible	0.00163%	61,222
European (non-Finnish)	0.0012%	83,401

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: EED
Protein: p.Ile44Val
Coding: c.130A>G
MANE Select: NM_003797
dbSNP: rs749513327
Type: single nucleotide variant
Location: chr11:86250311 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.21 · 81 PDB
Residue 44: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EED p.Ile44Thr Uncertain significance ★ ⚠ same residue
EED c.268-3T>C Conflicting classifications of pathogenicity ★ same condition
EED p.Ala327Ser Uncertain significance ★ ⚠ same condition
EED p.Ala41Thr Uncertain significance ★ ⚠ same condition
EED p.Arg4Ser Uncertain significance ★ ⚠ same condition
EED p.Asn102Asp Uncertain significance ★ ⚠ same condition
EED p.Asn266Thr Uncertain significance ★ ⚠ same condition
EED p.Asn272Ser 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/eed-p-ile44val (accessed [today's date]).

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