Is ERBIN p.Arg1076= (c.3228A>G) pathogenic?

ERBIN p.Arg1076= (c.3228A>G) is classified Benign in ERBIN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 45.1%, eas) — too common for a highly-penetrant pathogenic allele.

ERBIN p.Arg1076=

Q: How common is ERBIN p.Arg1076= (c.3228A>G) in the general population?

ERBIN p.Arg1076= (c.3228A>G) is common (popmax 45.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3228A>G · rs36303 · VCV1169279

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 45.1%, eas) — too common for a highly-penetrant pathogenic allele

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 3.1	GERP 1.9, phastCons 1
Overall
CADD	5.636	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 45.1% East Asian · 20,243/44,856 alleles

Filtering AF 44.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 44.4%

Overall 15.2% 244,676/1,614,024 alleles · common exomes 220,940/1,461,870 · genomes 23,736/152,154 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	45.1%	2
Admixed American	38.8%	3
Ashkenazi Jewishnot grpmax-eligible	25.5%	4
Remaining individualsnot grpmax-eligible	16.5%	6
Amishnot grpmax-eligible	16.2%	6
South Asian	15%	7
Finnishnot grpmax-eligible	14.9%	7
Middle Eastern	14.7%	7
European (non-Finnish)	12.9%	8
African / African-American	9.31%	11

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: ERBIN
Protein: p.Arg1076=
Coding: c.3228A>G
MANE Select: NM_001253697
dbSNP: rs36303
Type: single nucleotide variant
Location: chr5:66054546 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 56.01 · 11 PDB
Residue 1076: the 'disordered' region

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

Similar variants

ERBIN p.Arg1076Leu Uncertain significance ★ ⚠ same residue
ERBIN p.Arg1076Gln Uncertain significance ★★ same residue
ERBIN p.Ala942Val Uncertain significance ★★ ⚠ same type
ERBIN p.Arg1096Gln Uncertain significance ★★ ⚠ same type
ERBIN p.Arg1166Gln Uncertain significance ★★ ⚠ same type
ERBIN p.Asn1035Ser Uncertain significance ★★ ⚠ same type
ERBIN p.Asn650Ser Uncertain significance ★★ ⚠ same type
ERBIN p.Asp530Tyr 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/erbin-p-arg1076 (accessed [today's date]).

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