Is ENG p.Ala11= (c.33C>T) pathogenic?

ENG p.Ala11= (c.33C>T) is classified Likely benign in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-11). Very rare (popmax 0.00228%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Ala11= (c.33C>T)?

ENG p.Ala11= (c.33C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ENG p.Ala11= (c.33C>T) in the general population?

ENG p.Ala11= (c.33C>T) is very rare (popmax 0.00228%, eas) (gnomAD).

ENG p.Ala11=

c.33C>T · rs1217908512 · VCV1731024

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00228%, eas)

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 5.5	GERP 2.6, phastCons 1
Overall
CADD	9.531	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00228% East Asian · 1/43,888 alleles

Overall 0.000251% 4/1,596,400 alleles · very rare exomes 4/1,444,076 · genomes 0/152,324 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00228%	43,888
Remaining individualsnot grpmax-eligible	0.00162%	61,668
African / African-American	0.00134%	74,676
European (non-Finnish)	8.53e-05%	1,172,186

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.Ala11=
Coding: c.33C>T
MANE Select: NM_001114753
dbSNP: rs1217908512
Type: single nucleotide variant
Location: chr9:127854323 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 11: a UniProt-annotated variant site (in hht1)

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

Similar variants

ENG p.Ala11Val Uncertain significance ★ ⚠ same residue
ENG c.1134+1G>T Pathogenic/Likely pathogenic ★★ same condition
ENG c.1311+2T>A Pathogenic ★★ same condition
ENG c.1428+1G>A Pathogenic/Likely pathogenic ★★ same condition
ENG c.1687-1G>A Pathogenic/Likely pathogenic ★★ same condition
ENG c.219+1G>A Pathogenic ★★ same condition
ENG c.219+2T>C Pathogenic/Likely pathogenic ★★ same condition
ENG c.360+1G>A 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-ala11 (accessed [today's date]).

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