Is ENG p.Ser473= (c.1419C>T) pathogenic?

ENG p.Ser473= (c.1419C>T) is classified Benign/Likely benign in ENG (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). Rare (popmax 0.719%, sas); Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG p.Ser473= (c.1419C>T)?

ENG p.Ser473= (c.1419C>T) is associated with hereditary hemorrhagic telangiectasia, telangiectasia, hereditary hemorrhagic, type 1 (ClinVar).

How common is ENG p.Ser473= (c.1419C>T) in the general population?

ENG p.Ser473= (c.1419C>T) is rare (popmax 0.719%, sas) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

ENG p.Ser473=

c.1419C>T · rs561818608 · VCV365087

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.719%, sas)

Conditions

hereditary hemorrhagic telangiectasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.88 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.2	GERP -0.67, phastCons 1
Overall
CADD	8.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.719% South Asian · 655/91,080 alleles

Filtering AF 0.674% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.655%

Overall 0.0426% 688/1,614,142 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.719%	139
Remaining individualsnot grpmax-eligible	0.0448%	2,232
African / African-American	0.00133%	75,056
European (non-Finnish)	0.000339%	295,002

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.Ser473=
Coding: c.1419C>T
MANE Select: NM_001114753
dbSNP: rs561818608
Type: single nucleotide variant
Location: chr9:127818725 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 473: a β-strand; the zp domain

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

Also linked: telangiectasia, hereditary hemorrhagic, type 1

For Hereditary hemorrhagic telangiectasia (Orphanet):

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

Similar variants

ENG p.Ser473Arg 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
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-ser473 (accessed [today's date]).

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