Is EPHB1 p.Ile561= (c.1683C>T) pathogenic?

EPHB1 p.Ile561= (c.1683C>T) is classified Benign in EPHB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-01). Ultra-rare (popmax 0.0834%, sas).

How common is EPHB1 p.Ile561= (c.1683C>T) in the general population?

EPHB1 p.Ile561= (c.1683C>T) is ultra-rare (popmax 0.0834%, sas) (gnomAD).

EPHB1 p.Ile561=

c.1683C>T · rs192495343 · VCV724880

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0834%, sas)

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 -2.7	GERP -1.6
Overall
CADD	9.383	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0834% South Asian · 76/91,074 alleles

Filtering AF 0.0683% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0628%

Overall 0.103% 1,655/1,613,622 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.77%	57
Remaining individualsnot grpmax-eligible	0.13%	771
South Asiangrpmax	0.0834%	1,198
Middle Eastern	0.0495%	2,021
European (non-Finnish)	0.0295%	3,390
Admixed American	0.02%	5,002
African / African-American	0.004%	25,003
East Asian	0.00223%	44,868

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EPHB1
Protein: p.Ile561=
Coding: c.1683C>T
MANE Select: NM_004441
dbSNP: rs192495343
Type: single nucleotide variant
Location: chr3:135166065 (GRCh38)
Gene constraint: LOEUF 0.441 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.95 · 8 PDB

Full EPHB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHB1 p.Phe552= Benign/Likely benign ★★ same type
EPHB1 p.Thr981= Benign ★★ same type
EPHB1 c.2347-1G>A Uncertain significance ★ same type
EPHB1 p.Ala12Ser Uncertain significance ★ ⚠ same type
EPHB1 p.Ala132Gly Uncertain significance ★ ⚠ same type
EPHB1 p.Ala182Thr Uncertain significance ★ ⚠ same type
EPHB1 p.Ala39Val Uncertain significance ★ ⚠ same type
EPHB1 p.Ala547Val 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/ephb1-p-ile561 (accessed [today's date]).

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