Is ENG p.Gly40= (c.120C>T) pathogenic?

ENG p.Gly40= (c.120C>T) is classified Benign/Likely benign in ENG (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-05-01). Rare (popmax 0.629%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Gly40= (c.120C>T)?

ENG p.Gly40= (c.120C>T) is associated with Cardiovascular phenotype, telangiectasia, hereditary hemorrhagic, type 1, hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Gly40= (c.120C>T) in the general population?

ENG p.Gly40= (c.120C>T) is rare (popmax 0.629%, nfe) (gnomAD).

ENG p.Gly40=

c.120C>T · rs41522944 · VCV237016

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

rare (popmax 0.629%, nfe)

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 -0.76	GERP -3.1
Overall
CADD	4.341	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.629% European (non-Finnish) · 7,423/1,180,034 alleles

Filtering AF 0.617% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.612%

Overall 0.506% 8,164/1,614,206 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.629%	159
Remaining individualsnot grpmax-eligible	0.443%	226
Admixed American	0.415%	241
African / African-American	0.107%	938
South Asian	0.0988%	1,012
Ashkenazi Jewishnot grpmax-eligible	0.0946%	1,057
Middle Eastern	0.0495%	2,021
Finnishnot grpmax-eligible	0.0203%	4,925
East Asian	0.00223%	44,888

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.Gly40=
Coding: c.120C>T
MANE Select: NM_001114753
dbSNP: rs41522944
Type: single nucleotide variant
Location: chr9:127843193 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 40: a disulfide bond; the 'required for interaction with gdf2' region; the 'or1, n-terminal part' 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: telangiectasia, hereditary hemorrhagic, type 1 hereditary hemorrhagic telangiectasia

Similar variants

ENG p.Gly40Cys Likely benign ★★ ⚠ same residue
ENG p.Gly40fs Pathogenic ★ same residue
ENG p.Gly40_Thr45delinsAla 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

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-gly40 (accessed [today's date]).

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