Is ENG c.-343C>T pathogenic?

ENG c.-343C>T is classified Likely benign in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Rare (popmax 0.472%, eas); Associated with telangiectasia, hereditary hemorrhagic, type 1.

What condition is associated with ENG c.-343C>T?

ENG c.-343C>T is associated with telangiectasia, hereditary hemorrhagic, type 1 (ClinVar).

How common is ENG c.-343C>T in the general population?

ENG c.-343C>T is rare (popmax 0.472%, eas) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

ENG c.-343C>T

rs543301425 · VCV365108

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.472%, eas)

Conditions

telangiectasia, hereditary hemorrhagic, type 1

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 7.3	GERP 1.1, phastCons 1
Non-coding constraint	Z 3.30	1 kb window · o/e 0.70 · regional · uncalibrated
Overall
CADD	15.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.472% East Asian · 134/28,360 alleles

Filtering AF 0.407% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.383%

Overall 0.0369% 157/425,712 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.472%	212
Remaining individualsnot grpmax-eligible	0.0402%	2,486
South Asian	0.0152%	6,565
Admixed American	0.0126%	7,944
African / African-American	0.00615%	16,269
European (non-Finnish)	0.00288%	34,683

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
Coding: c.-343C>T
MANE Select: NM_001114753 · reported on NM_000118
dbSNP: rs543301425
Type: single nucleotide variant
Location: chr9:127854698 (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

telangiectasia, hereditary hemorrhagic, type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary hemorrhagic telangiectasia (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

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-c-minus-343c-t (accessed [today's date]).

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