Is ERBIN p.Pro292= (c.876A>G) pathogenic?

ERBIN p.Pro292= (c.876A>G) is classified Likely benign in ERBIN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0866%, nfe).

How common is ERBIN p.Pro292= (c.876A>G) in the general population?

ERBIN p.Pro292= (c.876A>G) is ultra-rare (popmax 0.0866%, nfe) (gnomAD).

ERBIN p.Pro292=

c.876A>G · rs143695017 · VCV735682

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0866%, nfe)

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 4.7	GERP 2.8, phastCons 1
Overall
CADD	10.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0866% European (non-Finnish) · 1,021/1,178,402 alleles

Filtering AF 0.0822% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0804%

Overall 0.0741% 1,194/1,612,052 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.223%	448
European (non-Finnish)grpmax	0.0866%	1,154
Remaining individualsnot grpmax-eligible	0.0833%	1,201
Admixed American	0.0683%	1,463
African / African-American	0.0173%	5,769
Middle Eastern	0.0166%	6,024

Ashkenazi Jewish 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: ERBIN
Protein: p.Pro292=
Coding: c.876A>G
MANE Select: NM_001253697
dbSNP: rs143695017
Type: single nucleotide variant
Location: chr5:66025538 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 56.01 · 11 PDB

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

Similar variants

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
ERBIN p.Cys658Ser Uncertain significance ★★ ⚠ same type
ERBIN p.His521Arg 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-pro292 (accessed [today's date]).

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