Is EPHB2 p.Val263Ile (c.787G>A) pathogenic?

EPHB2 p.Val263Ile (c.787G>A) is classified Likely benign in EPHB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2013-01-01). AlphaMissense: likely benign (0.0783); Ultra-rare (popmax 0.0253%, sas); Associated with Peters anomaly.

What condition is associated with EPHB2 p.Val263Ile (c.787G>A)?

EPHB2 p.Val263Ile (c.787G>A) is associated with Peters anomaly (ClinVar).

How common is EPHB2 p.Val263Ile (c.787G>A) in the general population?

EPHB2 p.Val263Ile (c.787G>A) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

What do computational predictors say about EPHB2 p.Val263Ile (c.787G>A)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

EPHB2 p.Val263Ile

c.787G>A · rs150803261 · VCV221961

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Peters anomaly

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -7.25	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 6.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 203 kb · p 2.4e-23 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% South Asian · 23/91,084 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00428% 69/1,613,620 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
African / African-American	0.012%	8,342
Remaining individualsnot grpmax-eligible	0.0048%	20,835
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Finnishnot grpmax-eligible	0.00315%	31,703
European (non-Finnish)	0.00254%	39,335
East Asian	0.00223%	44,888

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: EPHB2
Protein: p.Val263Ile
Coding: c.787G>A
MANE Select: NM_017449
dbSNP: rs150803261
Type: single nucleotide variant
Location: chr1:22785052 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 5 PDB

Full EPHB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Peters anomaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EPHB2 p.Val414Ile Uncertain significance ★★ ⚠ same type
EPHB2 c.1766-9G>T Benign/Likely benign ★★ same type
EPHB2 p.Ala279Ser Benign ★★ same type
EPHB2 p.Asn242= Likely benign ★★ same type
EPHB2 p.Asp574= Benign ★★ same type
EPHB2 p.Asp678Asn Likely benign ★★ ⚠ same type
EPHB2 p.Gln875= Benign ★★ same type
EPHB2 p.Ser170= Benign ★★ 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/ephb2-p-val263ile (accessed [today's date]).

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