Is ENG p.Thr557= (c.1671C>T) pathogenic?

ENG p.Thr557= (c.1671C>T) is classified Likely benign in ENG (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-07-23). Very rare (popmax 0.00534%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Thr557= (c.1671C>T)?

ENG p.Thr557= (c.1671C>T) is associated with Cardiovascular phenotype, hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Thr557= (c.1671C>T) in the general population?

ENG p.Thr557= (c.1671C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

ENG p.Thr557=

c.1671C>T · rs369135742 · VCV528076

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.14	GERP -1.8
Overall
CADD	7.704	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,942 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00223% 36/1,614,064 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,736
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.0022%	45,387
South Asian	0.0022%	45,545
Admixed American	0.00167%	60,012

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.Thr557=
Coding: c.1671C>T
dbSNP: rs369135742
Type: single nucleotide variant
Location: chr9:127818135 (GRCh38)

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

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-thr557 (accessed [today's date]).

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