Is EOGT p.Lys188Ter (c.562A>T) pathogenic?

EOGT p.Lys188Ter (c.562A>T) is classified Conflicting classifications of pathogenicity in EOGT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-01). Low-frequency (popmax 2.91%, afr); Associated with Adams-Oliver syndrome 4.

What condition is associated with EOGT p.Lys188Ter (c.562A>T)?

EOGT p.Lys188Ter (c.562A>T) is associated with Adams-Oliver syndrome 4 (ClinVar).

How common is EOGT p.Lys188Ter (c.562A>T) in the general population?

EOGT p.Lys188Ter (c.562A>T) is low-frequency (popmax 2.91%, afr) (gnomAD).

EOGT p.Lys188Ter

c.562A>T · rs116711473 · VCV445341

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 2.91%, afr)

Conditions

Adams-Oliver syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -4.4
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.91% African / African-American · 2,183/75,032 alleles

Filtering AF 2.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.77%

Overall 0.169% 2,722/1,614,144 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.91%	34
Admixed American	0.235%	426
Middle Eastern	0.181%	551
South Asian	0.167%	599
Remaining individualsnot grpmax-eligible	0.165%	607
European (non-Finnish)	0.0112%	8,939

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.Lys188Ter
Coding: c.562A>T
MANE Select: NM_001278689
dbSNP: rs116711473
Type: single nucleotide variant
Location: chr3:69004436 (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 p.Lys188Leu Benign ★★ same residue
EOGT p.Lys188Ile Likely benign ★★ same residue
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

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-lys188ter (accessed [today's date]).

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