Is SCRIB p.Ser1022= (c.3066C>T) pathogenic?

SCRIB p.Ser1022= (c.3066C>T) is classified Likely benign in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-04). Ultra-rare (popmax 0.0154%, sas); Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Ser1022= (c.3066C>T)?

SCRIB p.Ser1022= (c.3066C>T) is associated with SCRIB-related disorder (ClinVar).

How common is SCRIB p.Ser1022= (c.3066C>T) in the general population?

SCRIB p.Ser1022= (c.3066C>T) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

SCRIB p.Ser1022=

c.3066C>T · rs565642007 · VCV3048664

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Conditions

SCRIB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -11	GERP -3
Overall
CADD	0.239	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% South Asian · 14/90,966 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00736%

Overall 0.00322% 52/1,612,760 alleles · ultra-rare exomes 49/1,460,530 · genomes 3/152,230 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,498
Remaining individualsnot grpmax-eligible	0.0128%	7,802
African / African-American	0.00667%	14,987
European (non-Finnish)	0.00212%	47,180

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.Ser1022=
Coding: c.3066C>T
MANE Select: NM_182706
dbSNP: rs565642007
Type: single nucleotide variant
Location: chr8:143804100 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 1022: a β-strand; the pdz 3 domain; the 'interaction with arhgef7' region; the 'required for interaction with vim' region

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

Disease context

SCRIB-related disorder

Similar variants

SCRIB p.Ser1022Ala Uncertain significance ★ ⚠ same residue
SCRIB p.Ser1022Cys Uncertain significance ★ ⚠ same residue
SCRIB p.Arg231Gln Uncertain significance ★ ⚠ same condition
SCRIB c.2179-10C>T Likely benign same condition
SCRIB c.3714+7G>A Likely benign same condition
SCRIB c.4018-6C>T Likely benign same condition
SCRIB c.4514+8C>T Likely benign same condition
SCRIB c.4515-4G>A Likely benign 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/scrib-p-ser1022 (accessed [today's date]).

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