Is EOGT p.Ile355Val (c.1063A>G) pathogenic?

EOGT p.Ile355Val (c.1063A>G) is classified Uncertain significance in EOGT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-05). AlphaMissense: likely benign (0.0724); Very rare (popmax 0.000262%, nfe).

How common is EOGT p.Ile355Val (c.1063A>G) in the general population?

EOGT p.Ile355Val (c.1063A>G) is very rare (popmax 0.000262%, nfe) (gnomAD).

What do computational predictors say about EOGT p.Ile355Val (c.1063A>G)?

AlphaMissense predicts likely benign (score 0.0724) — an in-silico prediction, not a clinical call.

EOGT p.Ile355Val

c.1063A>G · VCV4540892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0724 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000262%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0724	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -5.88	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 0.3	GERP -0.2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 32 kb · p 0.016 · regional, not allelic
Overall
CADD	15.24	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 0.000262% European (non-Finnish) · 3/1,146,602 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000217% 3/1,383,440 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: EOGT
Protein: p.Ile355Val
Coding: c.1063A>G
MANE Select: NM_001278689
Type: single nucleotide variant
Location: chr3:68988315 (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

Similar variants

EOGT c.1335-1G>A Pathogenic/Likely pathogenic ★★ same type
EOGT c.311+1G>T Pathogenic/Likely pathogenic ★★ same type
EOGT c.621-2A>T Pathogenic/Likely pathogenic ★★ same type
EOGT p.Arg149His Uncertain significance ★★ ⚠ same type
EOGT p.Arg372Trp Uncertain significance ★★ ⚠ same type
EOGT p.Arg377Trp Uncertain significance ★★ ⚠ same type
EOGT p.Arg452His Uncertain significance ★★ ⚠ same type
EOGT p.Arg470Trp 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/eogt-p-ile355val (accessed [today's date]).

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