Is EPHB4 p.Gly264Arg (c.790G>A) pathogenic?

EPHB4 p.Gly264Arg (c.790G>A) is classified Uncertain significance in EPHB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-01). AlphaMissense: likely benign (0.2327); Absent from gnomAD v4.1.

How common is EPHB4 p.Gly264Arg (c.790G>A) in the general population?

EPHB4 p.Gly264Arg (c.790G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPHB4 p.Gly264Arg (c.790G>A)?

AlphaMissense predicts likely benign (score 0.2327) — an in-silico prediction, not a clinical call.

EPHB4 p.Gly264Arg

c.790G>A · rs2485044748 · VCV2780796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2327 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,563,110)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2327	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -6.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.00047 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,563,110). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EPHB4
Protein: p.Gly264Arg
Coding: c.790G>A
MANE Select: NM_004444
dbSNP: rs2485044748
Type: single nucleotide variant
Location: chr7:100822289 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 264: a UniProt-annotated variant site (in cmavm2)

Full EPHB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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EPHB4 p.Arg365Ter Pathogenic/Likely pathogenic ★★ same type
EPHB4 p.Arg394Ter Pathogenic ★★ same type
EPHB4 p.Arg431Ter Pathogenic ★★ same type
EPHB4 p.Arg739Gln Pathogenic ★★ same type
EPHB4 p.Arg739Ter Pathogenic ★★ 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/ephb4-p-gly264arg (accessed [today's date]).

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