Is ENG p.Gly598= (c.1794T>C) pathogenic?

ENG p.Gly598= (c.1794T>C) is classified Benign/Likely benign in ENG (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Low-frequency (popmax 4.31%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Gly598= (c.1794T>C)?

ENG p.Gly598= (c.1794T>C) is associated with Cardiovascular phenotype, telangiectasia, hereditary hemorrhagic, type 1, hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Gly598= (c.1794T>C) in the general population?

ENG p.Gly598= (c.1794T>C) is low-frequency (popmax 4.31%, afr) (gnomAD).

ENG p.Gly598=

c.1794T>C · rs41358947 · VCV213203

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.31%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3.8
Overall
CADD	5.277	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.31% African / African-American · 3,231/75,008 alleles

Filtering AF 4.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.13%

Overall 0.575% 9,266/1,610,468 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.31%	23
South Asian	3.42%	29
Amishnot grpmax-eligible	1.43%	70
Remaining individualsnot grpmax-eligible	0.655%	153
Admixed American	0.48%	208
Middle Eastern	0.319%	314
European (non-Finnish)	0.187%	535
East Asian	0.0246%	4,071
Finnishnot grpmax-eligible	0.0111%	9,033
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,486

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: ENG
Protein: p.Gly598=
Coding: c.1794T>C
MANE Select: NM_001114753
dbSNP: rs41358947
Type: single nucleotide variant
Location: chr9:127816001 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB

Full ENG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: telangiectasia, hereditary hemorrhagic, type 1 hereditary hemorrhagic telangiectasia

Similar variants

ENG p.Arg529His Pathogenic ★★★ ⚠ same condition
ENG p.Asn423Ser Likely pathogenic ★★★ ⚠ same condition
ENG p.Cys382Tyr Pathogenic ★★★ same condition
ENG p.Cys549Gly Likely pathogenic ★★★ same condition
ENG p.Gly331Ser Pathogenic ★★★ ⚠ same condition
ENG p.Gly603Arg Likely pathogenic ★★★ same condition
ENG p.Leu221Pro Likely pathogenic ★★★ same condition
ENG p.Leu506His 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/eng-p-gly598 (accessed [today's date]).

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