Is ERBIN p.Asp635fs (c.1902dup) pathogenic?

ERBIN p.Asp635fs (c.1902dup) is classified Uncertain significance in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). Very rare (popmax 0.000258%, nfe).

How common is ERBIN p.Asp635fs (c.1902dup) in the general population?

ERBIN p.Asp635fs (c.1902dup) is very rare (popmax 0.000258%, nfe) (gnomAD).

ERBIN p.Asp635fs

c.1902dup · rs1221795699 · VCV1957432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000258%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 19 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP 5, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000258% European (non-Finnish) · 3/1,161,042 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000191% 3/1,574,004 alleles · very rare

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.Asp635fs
Coding: c.1902dup
MANE Select: NM_001253697
dbSNP: rs1221795699
Type: Duplication
Location: chr5:66048774 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 56.01 · 11 PDB
Residue 635: the 'disordered' region

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

Similar variants

ERBIN p.Asp635= Likely benign ★ same residue
ERBIN c.4131+27dup Benign ★★ same type
ERBIN c.477-10dup Benign/Likely benign ★★ same type
ERBIN p.Ala754fs Uncertain significance ★ same type
ERBIN p.Gln335fs Uncertain significance ★ same type
ERBIN p.Met612_Arg613insLeu Uncertain significance ★ same type
ERBIN p.Ser6fs Uncertain significance ★ same type
ERBIN p.Thr1216fs 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-asp635fs (accessed [today's date]).

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