Is ERBIN p.Glu60Asp (c.180G>T) pathogenic?

ERBIN p.Glu60Asp (c.180G>T) is classified Uncertain significance in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.2251); Very rare (popmax 0.00727%, nfe).

How common is ERBIN p.Glu60Asp (c.180G>T) in the general population?

ERBIN p.Glu60Asp (c.180G>T) is very rare (popmax 0.00727%, nfe) (gnomAD).

What do computational predictors say about ERBIN p.Glu60Asp (c.180G>T)?

AlphaMissense predicts likely benign (score 0.2251) — an in-silico prediction, not a clinical call.

ERBIN p.Glu60Asp

c.180G>T · rs186555721 · VCV2713834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2251 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00727%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2251	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -9.16	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 2	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 56 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	22.1	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 0.00727% European (non-Finnish) · 85/1,169,714 alleles

Filtering AF 0.00601% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00554%

Overall 0.00568% 90/1,585,644 alleles · very rare exomes 86/1,433,398 · genomes 4/152,246 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00727%	13,761
Remaining individualsnot grpmax-eligible	0.00326%	30,651
East Asian	0.00225%	44,380
Admixed American	0.00187%	53,358
African / African-American	0.00136%	73,316

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.Glu60Asp
Coding: c.180G>T
MANE Select: NM_001253697
dbSNP: rs186555721
Type: single nucleotide variant
Location: chr5:65992898 (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-glu60asp (accessed [today's date]).

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