Is EID2 p.Gly76Arg (c.226G>A) pathogenic?

EID2 p.Gly76Arg (c.226G>A) is classified Uncertain significance in EID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). AlphaMissense: ambiguous (0.3853); Very rare (popmax 0.002%, nfe).

How common is EID2 p.Gly76Arg (c.226G>A) in the general population?

EID2 p.Gly76Arg (c.226G>A) is very rare (popmax 0.002%, nfe) (gnomAD).

What do computational predictors say about EID2 p.Gly76Arg (c.226G>A)?

AlphaMissense predicts ambiguous (score 0.3853) — an in-silico prediction, not a clinical call.

EID2 p.Gly76Arg

c.226G>A · VCV3507454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3853 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.002%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3853	ambiguous
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.85	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.70 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.6	GERP -2.2, phastCons 0.011
Regional constraint	o/e 0.84	unconstrained · MANE · 707 bp · p 0.0037 · regional, not allelic
Overall
CADD	13.33	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 0.002% European (non-Finnish) · 21/1,050,200 alleles

Filtering AF 0.00129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00165% 22/1,334,394 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.002%	50,010
Remaining individualsnot grpmax-eligible	0.00199%	50,282

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: EID2
Protein: p.Gly76Arg
Coding: c.226G>A
MANE Select: NM_153232
Type: single nucleotide variant
Location: chr19:39539854 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI 0.43 (gnomAD)
Structure: AlphaFold pLDDT 58.28

Full EID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EID2 p.Ala135Val Uncertain significance ★ ⚠ same type
EID2 p.Ala187Thr Uncertain significance ★ ⚠ same type
EID2 p.Ala194Gly Uncertain significance ★ ⚠ same type
EID2 p.Ala49Val Uncertain significance ★ ⚠ same type
EID2 p.Ala50Thr Uncertain significance ★ ⚠ same type
EID2 p.Ala77Val Uncertain significance ★ ⚠ same type
EID2 p.Arg110Pro Uncertain significance ★ ⚠ same type
EID2 p.Arg128Gly 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/eid2-p-gly76arg (accessed [today's date]).

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