Is ENG p.Thr544= (c.1632C>T) pathogenic?

ENG p.Thr544= (c.1632C>T) is classified Likely benign in ENG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-25). Rare (popmax 0.129%, eas); Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG p.Thr544= (c.1632C>T)?

ENG p.Thr544= (c.1632C>T) is associated with hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Thr544= (c.1632C>T) in the general population?

ENG p.Thr544= (c.1632C>T) is rare (popmax 0.129%, eas) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

ENG p.Thr544=

c.1632C>T · rs117510900 · VCV696743

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.129%, eas)

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 -3.2	GERP -3.2
Overall
CADD	0.796	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.129% East Asian · 58/44,886 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.093%

Overall 0.0103% 167/1,614,218 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.129%	774
European (non-Finnish)	0.00864%	11,569
African / African-American	0.00533%	18,767
Remaining individualsnot grpmax-eligible	0.0048%	20,835

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.Thr544=
Coding: c.1632C>T
MANE Select: NM_001114753
dbSNP: rs117510900
Type: single nucleotide variant
Location: chr9:127818174 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 544: a β-strand; a disulfide bond

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.Thr544fs Pathogenic ★ same residue
ENG p.Thr544Ile Uncertain significance ★ ⚠ 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

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-thr544 (accessed [today's date]).

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