Is EID2 p.Ile166Val (c.496A>G) pathogenic?

EID2 p.Ile166Val (c.496A>G) is classified Uncertain significance in EID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.1823); Ultra-rare (popmax 0.0165%, mid).

How common is EID2 p.Ile166Val (c.496A>G) in the general population?

EID2 p.Ile166Val (c.496A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about EID2 p.Ile166Val (c.496A>G)?

AlphaMissense predicts likely benign (score 0.1823) — an in-silico prediction, not a clinical call.

EID2 p.Ile166Val

c.496A>G · rs754498911 · VCV2219892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1823 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1823	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.15	GERP -1.9, phastCons 0.001
Regional constraint	o/e 0.84	unconstrained · MANE · 707 bp · p 0.0037 · regional, not allelic
Overall
CADD	14.74	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000821% 12/1,461,894 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Admixed American	0.0133%	7,503
South Asian	0.0022%	45,543
European (non-Finnish)	8.47e-05%	1,180,022

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.Ile166Val
Coding: c.496A>G
MANE Select: NM_153232
dbSNP: rs754498911
Type: single nucleotide variant
Location: chr19:39539584 (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-ile166val (accessed [today's date]).

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