Is ERBIN p.Pro1285Ala (c.3853C>G) pathogenic?

ERBIN p.Pro1285Ala (c.3853C>G) is classified Uncertain significance in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely pathogenic (0.9009); Very rare (popmax 8.47e-05%, nfe); Associated with ERBIN-related disorder.

What condition is associated with ERBIN p.Pro1285Ala (c.3853C>G)?

ERBIN p.Pro1285Ala (c.3853C>G) is associated with ERBIN-related disorder (ClinVar).

How common is ERBIN p.Pro1285Ala (c.3853C>G) in the general population?

ERBIN p.Pro1285Ala (c.3853C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ERBIN p.Pro1285Ala (c.3853C>G)?

AlphaMissense predicts likely pathogenic (score 0.9009) — an in-silico prediction, not a clinical call.

ERBIN p.Pro1285Ala

c.3853C>G · rs778809727 · VCV2635898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9009 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ERBIN-related disorder

Computational evidence

Protein change
AlphaMissense	0.9009	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -6.89	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 30 kb · p 0.011 · regional, not allelic
Overall
CADD	23.6	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 8.47e-05% European (non-Finnish) · 1/1,180,008 alleles

Overall 6.2e-05% 1/1,614,142 alleles · very rare exomes 1/1,461,860 · genomes 0/152,282 · 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.Pro1285Ala
Coding: c.3853C>G
MANE Select: NM_001253697
dbSNP: rs778809727
Type: single nucleotide variant
Location: chr5:66075120 (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

Disease context

ERBIN-related disorder

Similar variants

ERBIN p.Ala942Val Uncertain significance ★★ ⚠ same condition
ERBIN p.Asn1035Ser Uncertain significance ★★ ⚠ same condition
ERBIN p.His587Arg Uncertain significance ★★ ⚠ same condition
ERBIN p.Ile318Thr Uncertain significance ★★ ⚠ same condition
ERBIN p.Ile318Val Uncertain significance ★★ ⚠ same condition
ERBIN p.Met289Ile Uncertain significance ★★ ⚠ same condition
ERBIN p.Pro339Ala Uncertain significance ★★ ⚠ same condition
ERBIN p.Tyr920Cys Uncertain significance ★★ ⚠ same condition

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-pro1285ala (accessed [today's date]).

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