Is ENG p.Ala243= (c.729A>C) pathogenic?

ENG p.Ala243= (c.729A>C) is classified Likely benign in ENG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-29). Ultra-rare (popmax 0.0134%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Ala243= (c.729A>C)?

ENG p.Ala243= (c.729A>C) is associated with Cardiovascular phenotype, hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Ala243= (c.729A>C) in the general population?

ENG p.Ala243= (c.729A>C) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

ENG p.Ala243=

c.729A>C · rs1242657224 · VCV1106562

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, 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 -2.7	GERP -3.1
Overall
CADD	1.234	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% African / African-American · 9/67,396 alleles

Filtering AF 0.00696% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00513%

Overall 0.00264% 42/1,589,204 alleles · ultra-rare exomes 13/1,460,804 · genomes 29/128,400 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,488
Admixed American	0.00529%	18,909
South Asian	0.00445%	22,456
European (non-Finnish)	0.00222%	45,046

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.Ala243=
Coding: c.729A>C
MANE Select: NM_001114753
dbSNP: rs1242657224
Type: single nucleotide variant
Location: chr9:127825318 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 243: 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: hereditary hemorrhagic telangiectasia

Similar variants

ENG p.Ala243Glu Uncertain significance ★ ⚠ same residue
ENG p.Ala243Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
ENG p.Ala243Val 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-ala243 (accessed [today's date]).

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