Is EOGT p.His27fs (c.78_81del) pathogenic?

EOGT p.His27fs (c.7881del) is classified Pathogenic/Likely pathogenic in EOGT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-29). Ultra-rare (popmax 0.0165%, mid); Associated with EOGT-related disorder.

What condition is associated with EOGT p.His27fs (c.78_81del)?

EOGT p.His27fs (c.78_81del) is associated with EOGT-related disorder, Adams-Oliver syndrome 4 (ClinVar).

How common is EOGT p.His27fs (c.78_81del) in the general population?

EOGT p.His27fs (c.78_81del) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

EOGT p.His27fs

c.78_81del · rs771160630 · VCV523593

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

EOGT-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -3.6
Overall
CADD	16.48	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00842% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00787%

Overall 0.00892% 144/1,614,144 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,250
Finnishnot grpmax-eligible	0.0125%	8,003
European (non-Finnish)	0.00992%	10,086
Admixed American	0.005%	20,008
African / African-American	0.004%	25,014
South Asian	0.0022%	45,542

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.His27fs
Coding: c.78_81del
MANE Select: NM_001278689
dbSNP: rs771160630
Type: Deletion
Location: chr3:69009766 (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

EOGT-related disorder

Also linked: Adams-Oliver syndrome 4

Similar variants

EOGT p.His27Tyr Uncertain significance ★ ⚠ same residue
EOGT p.Gly359fs Pathogenic/Likely pathogenic ★★ same condition
EOGT c.621-14del Likely benign ★★ same condition
EOGT c.924+1del Likely pathogenic ★ same condition
EOGT p.Leu66fs Pathogenic ★ same condition
EOGT c.1152+10del Benign ★ same condition
EOGT c.311+12del Likely benign ★ same condition
EOGT c.1335-1G>A Pathogenic/Likely pathogenic ★★ 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-his27fs (accessed [today's date]).

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