Is SCRIB p.Glu30Gln (c.88G>C) pathogenic?

SCRIB p.Glu30Gln (c.88G>C) is classified Uncertain significance in SCRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-03). AlphaMissense: likely pathogenic (0.8926); Very rare (popmax 0.000596%, nfe).

How common is SCRIB p.Glu30Gln (c.88G>C) in the general population?

SCRIB p.Glu30Gln (c.88G>C) is very rare (popmax 0.000596%, nfe) (gnomAD).

What do computational predictors say about SCRIB p.Glu30Gln (c.88G>C)?

AlphaMissense predicts likely pathogenic (score 0.8926) — an in-silico prediction, not a clinical call.

SCRIB p.Glu30Gln

c.88G>C · VCV4901855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8926 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000596%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8926	likely pathogenic
REVEL	0.121	moderately benign-leaning
SaProt	LLR -11.74	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 0.081, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,447 bp · p 0.0026 · regional, not allelic
Overall
CADD	23.9	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 0.000596% European (non-Finnish) · 7/1,174,744 alleles

Filtering AF 0.000248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000438% 7/1,597,242 alleles · very rare exomes 7/1,444,898 · genomes 0/152,344 · joint denominator

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: SCRIB
Protein: p.Glu30Gln
Coding: c.88G>C
MANE Select: NM_182706
Type: single nucleotide variant
Location: chr8:143815285 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 30: the 'disordered' region; the 'sufficient for targeting to adherens junction and to inhibit cell proliferation' region

Full SCRIB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCRIB p.Glu30Asp Uncertain significance ★ ⚠ same residue
SCRIB c.3120+10C>G Benign/Likely benign ★★ same type
SCRIB c.504-9C>T Benign ★★ same type
SCRIB p.Ala1488= Likely benign ★★ same type
SCRIB p.Arg492= Benign ★★ same type
SCRIB p.Asn647= Benign/Likely benign ★★ same type
SCRIB p.Leu254= Benign ★★ same type
SCRIB p.Phe571= Benign ★★ 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/scrib-p-glu30gln (accessed [today's date]).

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