Is ENG p.Ala511Val (c.1532C>T) pathogenic?

ENG p.Ala511Val (c.1532C>T) is classified Conflicting classifications of pathogenicity in ENG (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-16). AlphaMissense: likely benign (0.0861); Very rare (popmax 0.00799%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Ala511Val (c.1532C>T)?

ENG p.Ala511Val (c.1532C>T) is associated with Cardiovascular phenotype, hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Ala511Val (c.1532C>T) in the general population?

ENG p.Ala511Val (c.1532C>T) is very rare (popmax 0.00799%, afr) (gnomAD).

What do computational predictors say about ENG p.Ala511Val (c.1532C>T)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

ENG p.Ala511Val

c.1532C>T · rs200224098 · VCV1986841

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00799%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -6.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.027	GERP -3.2
Regional constraint	o/e 0.86	unconstrained · MANE · 39 kb · p 5.2e-05 · regional, not allelic
Overall
CADD	7.502	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00799% African / African-American · 6/75,054 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00105% 17/1,614,140 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00799%	12,509
Admixed American	0.00167%	60,024
Remaining individualsnot grpmax-eligible	0.0016%	62,510
South Asian	0.0011%	91,084
European (non-Finnish)	0.000678%	147,504

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.Ala511Val
Coding: c.1532C>T
MANE Select: NM_001114753
dbSNP: rs200224098
Type: single nucleotide variant
Location: chr9:127818274 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 511: a disulfide bond; the zp domain

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.Ala511= Benign/Likely benign ★★ same residue
ENG p.Ala511fs Pathogenic ★ 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-ala511val (accessed [today's date]).

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