Is ENG p.Met183Val (c.547A>G) pathogenic?

ENG p.Met183Val (c.547A>G) is classified Uncertain significance in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-08). AlphaMissense: likely benign (0.0626); Absent from gnomAD v4.1; Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG p.Met183Val (c.547A>G)?

ENG p.Met183Val (c.547A>G) is associated with hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Met183Val (c.547A>G) in the general population?

ENG p.Met183Val (c.547A>G) 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.Met183Val (c.547A>G)?

AlphaMissense predicts likely benign (score 0.0626) — an in-silico prediction, not a clinical call.

ENG p.Met183Val

c.547A>G · rs1830603171 · VCV835751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0626 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,756)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary hemorrhagic telangiectasia

Computational evidence

Protein change
AlphaMissense	0.0626	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -4.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.9	GERP -3.7
Regional constraint	o/e 0.86	unconstrained · MANE · 39 kb · p 5.2e-05 · regional, not allelic
Overall
CADD	0.024	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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 1,596,756). 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.Met183Val
Coding: c.547A>G
MANE Select: NM_001114753
dbSNP: rs1830603171
Type: single nucleotide variant
Location: chr9:127825837 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 183: a disulfide bond; the 'required for interaction with gdf2' region; the 'or2' region

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

For Hereditary hemorrhagic telangiectasia (Orphanet):

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

Similar variants

ENG p.Met183Ile 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-met183val (accessed [today's date]).

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