ENG p.Thr349=
c.1047T>C · rs1554810058 · VCV435059
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Conditions
2
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 -0.4 | GERP -3.5 |
| Overall | ||
| CADD | 6.128 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,074 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.00041%
6/1,461,864 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,074 |
| European (non-Finnish) | 0.000424% | 235,998 |
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.Thr349=
- Coding
- c.1047T>C
- MANE Select
- NM_001114753
- dbSNP
- rs1554810058
- Type
- single nucleotide variant
- Location
- chr9:127824391 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.84 · 3 PDB
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-thr349 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown