Is EFNB2 p.Tyr73Ter (c.219T>G) pathogenic?

EFNB2 p.Tyr73Ter (c.219T>G) is classified Likely pathogenic in EFNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-22). Absent from gnomAD v4.1.

How common is EFNB2 p.Tyr73Ter (c.219T>G) in the general population?

EFNB2 p.Tyr73Ter (c.219T>G) is absent from gnomAD v4.1 (gnomAD).

EFNB2 p.Tyr73Ter

c.219T>G · rs1879182475 · VCV928785

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 0.88, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EFNB2
Protein: p.Tyr73Ter
Coding: c.219T>G
MANE Select: NM_004093
dbSNP: rs1879182475
Type: single nucleotide variant
Location: chr13:106512716 (GRCh38)
Gene constraint: LOEUF 0.261 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.60 · 10 PDB
Residue 73: a disulfide bond; an α-helix; the ephrin rbd domain

Full EFNB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFNB2 p.Ala157Thr Uncertain significance ★ ⚠ same type
EFNB2 p.Ala296Ser Uncertain significance ★ ⚠ same type
EFNB2 p.Arg156Lys Uncertain significance ★ ⚠ same type
EFNB2 p.Arg182His Uncertain significance ★ ⚠ same type
EFNB2 p.Arg253Gln Uncertain significance ★ ⚠ same type
EFNB2 p.Arg253Trp Uncertain significance ★ ⚠ same type
EFNB2 p.Arg277Cys Uncertain significance ★ same type
EFNB2 p.Arg5Gly Uncertain significance ★ ⚠ same type

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/efnb2-p-tyr73ter (accessed [today's date]).

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