Is ENG p.Thr5= (c.15G>A) pathogenic?

ENG p.Thr5= (c.15G>A) is classified Benign in ENG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-25). Ultra-rare (popmax 0.0194%, sas); Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG p.Thr5= (c.15G>A)?

ENG p.Thr5= (c.15G>A) is associated with hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Thr5= (c.15G>A) in the general population?

ENG p.Thr5= (c.15G>A) is ultra-rare (popmax 0.0194%, sas) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

ENG p.Thr5=

c.15G>A · rs754570127 · VCV2789096

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, sas)

Conditions

hereditary hemorrhagic telangiectasia

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 -3.7	GERP -5.2
Overall
CADD	3.935	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0194% South Asian · 17/87,708 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00153% 22/1,441,470 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0194%	5,159
Admixed American	0.00701%	14,274
European (non-Finnish)	8.54e-05%	1,170,783

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.Thr5=
Coding: c.15G>A
MANE Select: NM_001114753
dbSNP: rs754570127
Type: single nucleotide variant
Location: chr9:127854341 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 5: a UniProt-annotated variant site (in)

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

Disease context

hereditary hemorrhagic telangiectasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary hemorrhagic telangiectasia (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ENG p.Thr5Met Benign/Likely benign ★★ 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-thr5 (accessed [today's date]).

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