Is EOGT p.Ile466Val (c.1396A>G) pathogenic?

EOGT p.Ile466Val (c.1396A>G) is classified Uncertain significance in EOGT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-24). AlphaMissense: likely benign (0.0553); Very rare (popmax 0.00502%, amr); Associated with Inborn genetic diseases.

What condition is associated with EOGT p.Ile466Val (c.1396A>G)?

EOGT p.Ile466Val (c.1396A>G) is associated with Inborn genetic diseases, Adams-Oliver syndrome 4 (ClinVar).

How common is EOGT p.Ile466Val (c.1396A>G) in the general population?

EOGT p.Ile466Val (c.1396A>G) is very rare (popmax 0.00502%, amr) (gnomAD).

What do computational predictors say about EOGT p.Ile466Val (c.1396A>G)?

AlphaMissense predicts likely benign (score 0.0553) — an in-silico prediction, not a clinical call.

EOGT p.Ile466Val

c.1396A>G · rs775338549 · VCV2082730

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0553 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0553	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -4.56	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 -5.5	GERP -4.3
Regional constraint	o/e 1.10	unconstrained · MANE · 32 kb · p 0.016 · regional, not allelic
Overall
CADD	0.221	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 0.00502% Admixed American · 3/59,814 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000868% 14/1,612,966 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00502%	19,938
European (non-Finnish)	0.000932%	107,239

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: EOGT
Protein: p.Ile466Val
Coding: c.1396A>G
MANE Select: NM_001278689
dbSNP: rs775338549
Type: single nucleotide variant
Location: chr3:68978374 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.71

Full EOGT 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

Also linked: Adams-Oliver syndrome 4

Similar variants

EOGT c.1335-1G>A Pathogenic/Likely pathogenic ★★ same condition
EOGT c.311+1G>T Pathogenic/Likely pathogenic ★★ same condition
EOGT c.621-2A>T Pathogenic/Likely pathogenic ★★ same condition
EOGT p.Arg149His Uncertain significance ★★ ⚠ same condition
EOGT p.Arg372Trp Uncertain significance ★★ ⚠ same condition
EOGT p.Arg377Trp Uncertain significance ★★ ⚠ same condition
EOGT p.Arg452His Uncertain significance ★★ ⚠ same condition
EOGT p.Arg470Trp 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/eogt-p-ile466val (accessed [today's date]).

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