Is EID3 p.Glu72Lys (c.214G>A) pathogenic?

EID3 p.Glu72Lys (c.214G>A) is classified Uncertain significance in EID3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely benign (0.1019); Rare (popmax 0.285%, nfe).

How common is EID3 p.Glu72Lys (c.214G>A) in the general population?

EID3 p.Glu72Lys (c.214G>A) is rare (popmax 0.285%, nfe) (gnomAD).

What do computational predictors say about EID3 p.Glu72Lys (c.214G>A)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

EID3 p.Glu72Lys

c.214G>A · rs201074393 · VCV3087837

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.285%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -3.79	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 7.5	GERP 1.2, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 998 bp · p 0.0026 · regional, not allelic
Overall
CADD	23.5	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 0.285% European (non-Finnish) · 3,362/1,179,914 alleles

Filtering AF 0.277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.274%

Overall 0.219% 3,542/1,613,978 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.285%	351
Remaining individualsnot grpmax-eligible	0.158%	631
Finnishnot grpmax-eligible	0.0453%	2,208
African / African-American	0.044%	2,271
Middle Eastern	0.0329%	3,042
Admixed American	0.0117%	8,573
South Asian	0.00988%	10,122
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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: EID3
Protein: p.Glu72Lys
Coding: c.214G>A
MANE Select: NM_001008394
dbSNP: rs201074393
Type: single nucleotide variant
Location: chr12:104304148 (GRCh38)
Gene constraint: LOEUF 1.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.67 · 3 PDB

Full EID3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EID3 p.Glu72Val Uncertain significance ★ ⚠ same residue
EID3 p.Ala153Pro Uncertain significance ★ ⚠ same type
EID3 p.Ala216Val Uncertain significance ★ ⚠ same type
EID3 p.Ala319Val Uncertain significance ★ ⚠ same type
EID3 p.Ala326Val Uncertain significance ★ ⚠ same type
EID3 p.Ala62Val Uncertain significance ★ ⚠ same type
EID3 p.Ala9Pro Uncertain significance ★ ⚠ same type
EID3 p.Arg179Leu 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/eid3-p-glu72lys (accessed [today's date]).

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