Is ERBIN p.Pro13Ser (c.37C>T) pathogenic?

ERBIN p.Pro13Ser (c.37C>T) is classified Uncertain significance in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-26). AlphaMissense: likely pathogenic (0.937); Very rare (popmax 0.0084%, nfe).

How common is ERBIN p.Pro13Ser (c.37C>T) in the general population?

ERBIN p.Pro13Ser (c.37C>T) is very rare (popmax 0.0084%, nfe) (gnomAD).

What do computational predictors say about ERBIN p.Pro13Ser (c.37C>T)?

AlphaMissense predicts likely pathogenic (score 0.937) — an in-silico prediction, not a clinical call.

ERBIN p.Pro13Ser

c.37C>T · rs377154455 · VCV1907847

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.937 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0084%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.937	likely pathogenic
REVEL	0.336	indeterminate
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 56 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	27.4	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 0.0084% European (non-Finnish) · 99/1,179,206 alleles

Filtering AF 0.00703% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00652%

Overall 0.00645% 104/1,611,658 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0084%	11,911
Remaining individualsnot grpmax-eligible	0.00641%	15,595
African / African-American	0.00134%	74,790

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.Pro13Ser
Coding: c.37C>T
MANE Select: NM_001253697
dbSNP: rs377154455
Type: single nucleotide variant
Location: chr5:65992755 (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.Pro13= Likely benign ★ same residue
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

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-pro13ser (accessed [today's date]).

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