Is ENG p.Pro244= (c.732C>T) pathogenic?

ENG p.Pro244= (c.732C>T) is classified Benign/Likely benign in ENG (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). Rare (popmax 0.361%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Pro244= (c.732C>T)?

ENG p.Pro244= (c.732C>T) is associated with Cardiovascular phenotype, telangiectasia, hereditary hemorrhagic, type 1, hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Pro244= (c.732C>T) in the general population?

ENG p.Pro244= (c.732C>T) is rare (popmax 0.361%, afr) (gnomAD).

ENG p.Pro244=

c.732C>T · rs112262663 · VCV255146

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.361%, afr)

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 -7.9	GERP -3.1
Overall
CADD	0.908	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.361% African / African-American · 268/74,240 alleles

Filtering AF 0.325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.312%

Overall 0.0243% 392/1,611,264 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.361%	277
Remaining individualsnot grpmax-eligible	0.0496%	2,015
Admixed American	0.0436%	2,293
Middle Eastern	0.033%	3,028
European (non-Finnish)	0.00517%	19,337
South Asian	0.0044%	22,736

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.Pro244=
Coding: c.732C>T
MANE Select: NM_001114753
dbSNP: rs112262663
Type: single nucleotide variant
Location: chr9:127825315 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 244: a disulfide bond; 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: telangiectasia, hereditary hemorrhagic, type 1 hereditary hemorrhagic telangiectasia

Similar variants

ENG p.Pro244Ser Uncertain significance ★ ⚠ same residue
ENG p.Pro244Thr 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

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-pro244 (accessed [today's date]).

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