Is EOGT p.Val512Ile (c.1534G>A) pathogenic?

EOGT p.Val512Ile (c.1534G>A) is classified Uncertain significance in EOGT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-11). AlphaMissense: likely benign (0.0817); Very rare (popmax 0.00667%, amr); Associated with Adams-Oliver syndrome 4.

What condition is associated with EOGT p.Val512Ile (c.1534G>A)?

EOGT p.Val512Ile (c.1534G>A) is associated with Adams-Oliver syndrome 4 (ClinVar).

How common is EOGT p.Val512Ile (c.1534G>A) in the general population?

EOGT p.Val512Ile (c.1534G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about EOGT p.Val512Ile (c.1534G>A)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

EOGT p.Val512Ile

c.1534G>A · rs562651560 · VCV1984648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Adams-Oliver syndrome 4

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -8.53	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 2.6	GERP 1.1, phastCons 0.99
Regional constraint	o/e 1.10	unconstrained · MANE · 32 kb · p 0.016 · regional, not allelic
Overall
CADD	19.73	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 0.00667% Admixed American · 4/59,982 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00161% 26/1,613,904 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,995
African / African-American	0.00533%	18,753
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.00136%	73,746
South Asian	0.0011%	91,018

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.Val512Ile
Coding: c.1534G>A
MANE Select: NM_001278689
dbSNP: rs562651560
Type: single nucleotide variant
Location: chr3:68977668 (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

Adams-Oliver syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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.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
EOGT p.Asp252Asn 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-val512ile (accessed [today's date]).

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