Is ENG p.Thr617= (c.1851G>A) pathogenic?

ENG p.Thr617= (c.1851G>A) is classified Likely benign in ENG (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0501%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Thr617= (c.1851G>A)?

ENG p.Thr617= (c.1851G>A) is associated with Cardiovascular phenotype, hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Thr617= (c.1851G>A) in the general population?

ENG p.Thr617= (c.1851G>A) is ultra-rare (popmax 0.0501%, mid) (gnomAD).

ENG p.Thr617=

c.1851G>A · rs747344646 · VCV1098933

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0501%, mid)

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 -4.2	GERP -2.6
Overall
CADD	6.674	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0501% Middle Eastern · 3/5,986 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00727%

Overall 0.00226% 36/1,595,614 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0501%	1,995
South Asian	0.00567%	17,634
African / African-American	0.00401%	24,929
East Asian	0.00226%	44,220
European (non-Finnish)	0.00196%	50,952
Admixed American	0.00176%	56,974

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.Thr617=
Coding: c.1851G>A
MANE Select: NM_001114753
dbSNP: rs747344646
Type: single nucleotide variant
Location: chr9:127815944 (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: hereditary hemorrhagic telangiectasia

Similar variants

ENG p.Thr617Met Conflicting classifications of pathogenicity ★ same residue
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

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-thr617 (accessed [today's date]).

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