Is ENG p.Ile644= (c.1932C>T) pathogenic?

ENG p.Ile644= (c.1932C>T) is classified Benign/Likely benign in ENG (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-06-19). Common (popmax 13.6%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Ile644= (c.1932C>T)?

ENG p.Ile644= (c.1932C>T) is associated with Cardiovascular phenotype, telangiectasia, hereditary hemorrhagic, type 1 (ClinVar).

ENG p.Ile644=

Q: How common is ENG p.Ile644= (c.1932C>T) in the general population?

ENG p.Ile644= (c.1932C>T) is common (popmax 13.6%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1932C>T · rs181330955 · VCV226632

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 13.6%, amr) — too common for a highly-penetrant pathogenic allele

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 0.29	GERP -4.1, phastCons 0.93
Overall
CADD	10.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.6% Admixed American · 7,260/53,274 alleles

Filtering AF 13.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.3%

Overall 0.551% 8,599/1,559,734 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	13.6%	7
East Asian	1.14%	88
Remaining individualsnot grpmax-eligible	0.786%	127
African / African-American	0.231%	432
South Asian	0.151%	661
European (non-Finnish)	0.00708%	14,119

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.Ile644=
Coding: c.1932C>T
MANE Select: NM_001114753
dbSNP: rs181330955
Type: single nucleotide variant
Location: chr9:127815727 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 644: the 'disordered' 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

Similar variants

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
ENG p.Leu506His 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-ile644 (accessed [today's date]).

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