Is ENG p.Ser50= (c.150G>A) pathogenic?

ENG p.Ser50= (c.150G>A) is classified Likely benign in ENG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-15). Very rare (popmax 0.00445%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Ser50= (c.150G>A)?

ENG p.Ser50= (c.150G>A) is associated with Cardiovascular phenotype, hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Ser50= (c.150G>A) in the general population?

ENG p.Ser50= (c.150G>A) is very rare (popmax 0.00445%, eas) (gnomAD).

ENG p.Ser50=

c.150G>A · rs377129516 · VCV237019

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

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 -3.8	GERP -4.5
Overall
CADD	0.524	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,894 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00103% 15/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,447
Remaining individualsnot grpmax-eligible	0.0016%	62,512
South Asian	0.0011%	91,076
European (non-Finnish)	0.000932%	107,278

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.Ser50=
Coding: c.150G>A
MANE Select: NM_001114753
dbSNP: rs377129516
Type: single nucleotide variant
Location: chr9:127843163 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 50: a disulfide bond; the 'required for interaction with gdf2' region; the 'or2' region; a β-strand

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.Ser50Ter Pathogenic ★ same residue
ENG p.Ser50Leu 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

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-ser50 (accessed [today's date]).

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