Is ERBIN p.Glu253Asp (c.759A>C) pathogenic?

ERBIN p.Glu253Asp (c.759A>C) is classified Uncertain significance in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-03). AlphaMissense: likely benign (0.1794); Very rare (popmax 0.00696%, nfe).

How common is ERBIN p.Glu253Asp (c.759A>C) in the general population?

ERBIN p.Glu253Asp (c.759A>C) is very rare (popmax 0.00696%, nfe) (gnomAD).

What do computational predictors say about ERBIN p.Glu253Asp (c.759A>C)?

AlphaMissense predicts likely benign (score 0.1794) — an in-silico prediction, not a clinical call.

ERBIN p.Glu253Asp

c.759A>C · VCV3715801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1794 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00696%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1794	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -8.12	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 6.2	GERP 4.2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 56 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	23.8	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 0.00696% European (non-Finnish) · 82/1,178,222 alleles

Filtering AF 0.00572% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00516% 83/1,608,128 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00696%	14,369
Remaining individualsnot grpmax-eligible	0.00161%	62,274

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.Glu253Asp
Coding: c.759A>C
MANE Select: NM_001253697
Type: single nucleotide variant
Location: chr5:66024392 (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-glu253asp (accessed [today's date]).

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