Is ERBIN p.Pro339Ala (c.1015C>G) pathogenic?

ERBIN p.Pro339Ala (c.1015C>G) is classified Uncertain significance in ERBIN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-11). AlphaMissense: likely benign (0.061); Ultra-rare (popmax 0.0446%, eas); Associated with ERBIN-related disorder.

What condition is associated with ERBIN p.Pro339Ala (c.1015C>G)?

ERBIN p.Pro339Ala (c.1015C>G) is associated with ERBIN-related disorder (ClinVar).

How common is ERBIN p.Pro339Ala (c.1015C>G) in the general population?

ERBIN p.Pro339Ala (c.1015C>G) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

What do computational predictors say about ERBIN p.Pro339Ala (c.1015C>G)?

AlphaMissense predicts likely benign (score 0.061) — an in-silico prediction, not a clinical call.

ERBIN p.Pro339Ala

c.1015C>G · rs761113985 · VCV2631412

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.061 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ERBIN-related disorder

Computational evidence

Protein change
AlphaMissense	0.061	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -8.59	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 3.3	GERP 4.1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 56 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	19.18	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 0.0446% East Asian · 19/42,640 alleles

Filtering AF 0.0292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0243%

Overall 0.00127% 20/1,578,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,244
African / African-American	0.00138%	72,432

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.Pro339Ala
Coding: c.1015C>G
MANE Select: NM_001253697
dbSNP: rs761113985
Type: single nucleotide variant
Location: chr5:66025972 (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.Tyr920Cys Uncertain significance ★★ ⚠ same condition
ERBIN c.3634-3256A>G 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-pro339ala (accessed [today's date]).

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