Is ENG p.Gly413Val (c.1238G>T) pathogenic?

ENG p.Gly413Val (c.1238G>T) is classified Pathogenic in ENG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2000-07-01). AlphaMissense: likely pathogenic (0.8302); Absent from gnomAD v4.1; Associated with telangiectasia, hereditary hemorrhagic, type 1.

What condition is associated with ENG p.Gly413Val (c.1238G>T)?

ENG p.Gly413Val (c.1238G>T) is associated with telangiectasia, hereditary hemorrhagic, type 1 (ClinVar).

How common is ENG p.Gly413Val (c.1238G>T) in the general population?

ENG p.Gly413Val (c.1238G>T) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

What do computational predictors say about ENG p.Gly413Val (c.1238G>T)?

AlphaMissense predicts likely pathogenic (score 0.8302) — an in-silico prediction, not a clinical call.

ENG p.Gly413Val

c.1238G>T · rs121918401 · VCV16674

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8302 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

telangiectasia, hereditary hemorrhagic, type 1

Computational evidence

Protein change
AlphaMissense	0.8302	likely pathogenic ✓ concordant with ClinVar · top 9% in ENG
REVEL	0.895	moderately pathogenic-leaning
SaProt	LLR -14.01	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 3.2	GERP 0.52, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 39 kb · p 5.2e-05 · regional, not allelic
Overall
CADD	25.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ENG
Protein: p.Gly413Val
Coding: c.1238G>T
MANE Select: NM_001114753
dbSNP: rs121918401
Type: single nucleotide variant
Location: chr9:127819934 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 413: a disulfide bond; the zp domain; a UniProt-annotated variant site (in hht1)

Full ENG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

telangiectasia, hereditary hemorrhagic, type 1 — 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.Gly413Asp Likely benign ★ ⚠ 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-gly413val (accessed [today's date]).

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