Is ERBIN p.Asp523Val (c.1568A>T) pathogenic?

ERBIN p.Asp523Val (c.1568A>T) is classified Uncertain significance in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-09). AlphaMissense: likely benign (0.0793); Very rare (popmax 8.49e-05%, nfe).

How common is ERBIN p.Asp523Val (c.1568A>T) in the general population?

ERBIN p.Asp523Val (c.1568A>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about ERBIN p.Asp523Val (c.1568A>T)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

ERBIN p.Asp523Val

c.1568A>T · rs1369396014 · VCV1361617

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 5.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 56 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,468 alleles

Overall 6.23e-05% 1/1,604,300 alleles · very rare exomes 1/1,451,958 · genomes 0/152,342 · joint denominator

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.Asp523Val
Coding: c.1568A>T
MANE Select: NM_001253697
dbSNP: rs1369396014
Type: single nucleotide variant
Location: chr5:66044276 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 56.01 · 11 PDB
Residue 523: the 'disordered' region

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

Similar variants

ERBIN p.Asp523Gly 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
ERBIN p.Cys658Ser 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-asp523val (accessed [today's date]).

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