Is ENG p.Thr343= (c.1029C>T) pathogenic?

ENG p.Thr343= (c.1029C>T) is classified Benign/Likely benign in ENG (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 19.1%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Thr343= (c.1029C>T)?

ENG p.Thr343= (c.1029C>T) is associated with Cardiovascular phenotype, telangiectasia, hereditary hemorrhagic, type 1, hereditary hemorrhagic telangiectasia (ClinVar).

ENG p.Thr343=

Q: How common is ENG p.Thr343= (c.1029C>T) in the general population?

ENG p.Thr343= (c.1029C>T) is common (popmax 19.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1029C>T · rs3739817 · VCV137209

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 19.1%, sas) — 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 6	GERP 1.6, phastCons 1
Overall
CADD	12.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.1% South Asian · 17,381/91,072 alleles

Filtering AF 18.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.7%

Overall 8.49% 137,091/1,613,948 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	19.1%	5
Finnishnot grpmax-eligible	8.91%	11
Middle Eastern	8.66%	12
Admixed American	8.21%	12
Remaining individualsnot grpmax-eligible	8.2%	12
European (non-Finnish)	8.19%	12
Ashkenazi Jewishnot grpmax-eligible	6.2%	16
African / African-American	4.73%	21
East Asian	3.02%	33
Amishnot grpmax-eligible	1.32%	76

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.Thr343=
Coding: c.1029C>T
MANE Select: NM_001114753
dbSNP: rs3739817
Type: single nucleotide variant
Location: chr9:127824409 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB

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 hereditary hemorrhagic telangiectasia

Similar variants

ENG p.Thr343Ala 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
ENG p.Gly603Arg Likely pathogenic ★★★ same condition
ENG p.Leu221Pro 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-thr343 (accessed [today's date]).

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