Is ERBIN p.Glu477Val (c.1430A>T) pathogenic?

ERBIN p.Glu477Val (c.1430A>T) is classified Uncertain significance in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-13). AlphaMissense: likely pathogenic (0.7635); Very rare (popmax 8.68e-05%, nfe).

How common is ERBIN p.Glu477Val (c.1430A>T) in the general population?

ERBIN p.Glu477Val (c.1430A>T) is very rare (popmax 8.68e-05%, nfe) (gnomAD).

What do computational predictors say about ERBIN p.Glu477Val (c.1430A>T)?

AlphaMissense predicts likely pathogenic (score 0.7635) — an in-silico prediction, not a clinical call.

ERBIN p.Glu477Val

c.1430A>T · rs770325297 · VCV2702681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.68e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7635	likely pathogenic
REVEL	0.375	indeterminate
SaProt	LLR -5.57	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 6.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 56 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	29.3	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 8.68e-05% European (non-Finnish) · 1/1,151,572 alleles

Overall 0.00013% 2/1,543,218 alleles · very rare exomes 2/1,390,888 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00169%	59,216
European (non-Finnish)grpmax	8.68e-05%	1,151,572

Remaining individuals 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.Glu477Val
Coding: c.1430A>T
MANE Select: NM_001253697
dbSNP: rs770325297
Type: single nucleotide variant
Location: chr5:66044138 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 56.01 · 11 PDB
Residue 477: the 'disordered' region

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-glu477val (accessed [today's date]).

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