Is ENG p.Cys207Arg (c.619T>C) pathogenic?

ENG p.Cys207Arg (c.619T>C) is classified Pathogenic/Likely pathogenic in ENG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-04). AlphaMissense: likely pathogenic (0.9672); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Cys207Arg (c.619T>C)?

ENG p.Cys207Arg (c.619T>C) is associated with Cardiovascular phenotype, hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Cys207Arg (c.619T>C) in the general population?

ENG p.Cys207Arg (c.619T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ENG p.Cys207Arg (c.619T>C)?

AlphaMissense predicts likely pathogenic (score 0.9672) — an in-silico prediction, not a clinical call.

ENG p.Cys207Arg

c.619T>C · rs2131889169 · VCV1511806

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9672 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,072)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9672	likely pathogenic ✓ concordant with ClinVar · top 2% in ENG
REVEL	0.784	moderately pathogenic-leaning
SaProt	LLR -17.25	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 39 kb · p 5.2e-05 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,599,072). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ENG
Protein: p.Cys207Arg
Coding: c.619T>C
MANE Select: NM_001114753
dbSNP: rs2131889169
Type: single nucleotide variant
Location: chr9:127825765 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 207: a β-strand; a disulfide bond; a UniProt-annotated variant site (in hht1); the 'required for interaction with gdf2' region; the 'or1, c-terminal part' region

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.Cys207Ter Pathogenic ★★ same residue
ENG p.Cys207fs Pathogenic ★ same residue
ENG p.Cys207Phe Likely pathogenic ★ same residue
ENG p.Cys207Tyr Likely pathogenic ★ 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

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-cys207arg (accessed [today's date]).

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