Is EBNA1BP2 p.Pro76Arg (c.227C>G) pathogenic?

EBNA1BP2 p.Pro76Arg (c.227C>G) is classified Benign in EBNA1BP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-12-11). AlphaMissense: likely benign (0.1039); Rare (popmax 0.837%, nfe).

How common is EBNA1BP2 p.Pro76Arg (c.227C>G) in the general population?

EBNA1BP2 p.Pro76Arg (c.227C>G) is rare (popmax 0.837%, nfe) (gnomAD).

What do computational predictors say about EBNA1BP2 p.Pro76Arg (c.227C>G)?

AlphaMissense predicts likely benign (score 0.1039) — an in-silico prediction, not a clinical call.

EBNA1BP2 p.Pro76Arg

c.227C>G · rs11559316 · VCV777906

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1039 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.837%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1039	likely benign
REVEL	0.331	indeterminate
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.5	GERP 0.67, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,321 bp · p 0.53 · regional, not allelic
Overall
CADD	26.3	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 0.837% European (non-Finnish) · 9,873/1,180,020 alleles

Filtering AF 0.823% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.817%

Overall 0.753% 12,158/1,614,084 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.92%	52
European (non-Finnish)grpmax	0.837%	120
Remaining individualsnot grpmax-eligible	0.691%	145
Middle Eastern	0.643%	155
South Asian	0.376%	266
Ashkenazi Jewishnot grpmax-eligible	0.159%	630
Admixed American	0.152%	659
African / African-American	0.14%	714
East Asian	0.00223%	44,886

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: EBNA1BP2
Protein: p.Pro76Arg
Coding: c.227C>G
MANE Select: NM_006824
dbSNP: rs11559316
Type: single nucleotide variant
Location: chr1:43171575 (GRCh38)
Gene constraint: LOEUF 1.006 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.02 · 10 PDB
Residue 76: an α-helix

Full EBNA1BP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBNA1BP2 p.Asn290Ile Benign ★★ same type
EBNA1BP2 c.-14G>T Uncertain significance ★ same type
EBNA1BP2 p.Ala112Val Uncertain significance ★ ⚠ same type
EBNA1BP2 p.Ala141Gly Uncertain significance ★ ⚠ same type
EBNA1BP2 p.Ala141Thr Uncertain significance ★ same type
EBNA1BP2 p.Ala198Gly Uncertain significance ★ ⚠ same type
EBNA1BP2 p.Arg110Gly Uncertain significance ★ ⚠ same type
EBNA1BP2 p.Arg122His 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/ebna1bp2-p-pro76arg (accessed [today's date]).

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