Is EPHB2 p.Arg191His (c.572G>A) pathogenic?

EPHB2 p.Arg191His (c.572G>A) is classified Uncertain significance in EPHB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). AlphaMissense: likely benign (0.1713); Ultra-rare (popmax 0.0166%, sas).

How common is EPHB2 p.Arg191His (c.572G>A) in the general population?

EPHB2 p.Arg191His (c.572G>A) is ultra-rare (popmax 0.0166%, sas) (gnomAD).

What do computational predictors say about EPHB2 p.Arg191His (c.572G>A)?

AlphaMissense predicts likely benign (score 0.1713) — an in-silico prediction, not a clinical call.

EPHB2 p.Arg191His

c.572G>A · VCV3509360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1713 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1713	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -10.02	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.5, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 203 kb · p 2.4e-23 · regional, not allelic
Overall
CADD	31.0	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 0.0166% South Asian · 15/90,176 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00829%

Overall 0.00336% 54/1,605,954 alleles · ultra-rare exomes 49/1,453,700 · genomes 5/152,254 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0166%	6,012
Finnishnot grpmax-eligible	0.0111%	9,033
Remaining individualsnot grpmax-eligible	0.00483%	20,714
East Asian	0.00447%	22,393
European (non-Finnish)	0.0023%	43,521

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.Arg191His
Coding: c.572G>A
MANE Select: NM_017449
Type: single nucleotide variant
Location: chr1:22784837 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 5 PDB
Residue 191: the eph lbd domain; a β-strand

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

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-arg191his (accessed [today's date]).

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