Is EID2B p.Phe96Ile (c.286T>A) pathogenic?

EID2B p.Phe96Ile (c.286T>A) is classified Uncertain significance in EID2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely pathogenic (0.8286); Very rare (popmax 0.0011%, sas).

How common is EID2B p.Phe96Ile (c.286T>A) in the general population?

EID2B p.Phe96Ile (c.286T>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about EID2B p.Phe96Ile (c.286T>A)?

AlphaMissense predicts likely pathogenic (score 0.8286) — an in-silico prediction, not a clinical call.

EID2B p.Phe96Ile

c.286T>A · VCV4247627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8286 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8286	likely pathogenic · top 7% in EID2B
REVEL	0.057	moderately benign-leaning
SaProt	LLR -5.85	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 0.6	GERP -3.1, phastCons 0.075
Regional constraint	o/e 1.03	unconstrained · MANE · 482 bp · p 0.69 · regional, not allelic
Overall
CADD	18.35	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 0.0011% South Asian · 1/91,086 alleles

Overall 6.84e-05% 1/1,461,798 alleles · very rare

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: EID2B
Protein: p.Phe96Ile
Coding: c.286T>A
MANE Select: NM_152361
Type: single nucleotide variant
Location: chr19:39532517 (GRCh38)
Gene constraint: LOEUF 1.759 · pLI 0.24 (gnomAD)
Structure: AlphaFold pLDDT 70.26

Full EID2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EID2B p.Phe96Leu Likely benign ★ ⚠ same residue
EID2B p.Ala131Val Uncertain significance ★ ⚠ same type
EID2B p.Ala134Thr Uncertain significance ★ ⚠ same type
EID2B p.Ala143Ser Uncertain significance ★ ⚠ same type
EID2B p.Ala45Thr Uncertain significance ★ ⚠ same type
EID2B p.Ala45Val Uncertain significance ★ ⚠ same type
EID2B p.Arg119Lys Uncertain significance ★ ⚠ same type
EID2B p.Gln83Pro 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/eid2b-p-phe96ile (accessed [today's date]).

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