Is SCRIB p.Thr1142= (c.3426G>A) pathogenic?

SCRIB p.Thr1142= (c.3426G>A) is classified Likely benign in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-22). Ultra-rare (popmax 0.0416%, eas); Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Thr1142= (c.3426G>A)?

SCRIB p.Thr1142= (c.3426G>A) is associated with SCRIB-related disorder (ClinVar).

How common is SCRIB p.Thr1142= (c.3426G>A) in the general population?

SCRIB p.Thr1142= (c.3426G>A) is ultra-rare (popmax 0.0416%, eas) (gnomAD).

SCRIB p.Thr1142=

c.3426G>A · rs782309851 · VCV3050376

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0416%, eas)

Conditions

SCRIB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.061	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3
Overall
CADD	0.918	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0416% East Asian · 9/21,636 alleles

Filtering AF 0.0216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0161%

Overall 0.0121% 165/1,358,296 alleles · ultra-rare exomes 144/1,219,158 · genomes 21/139,138 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0416%	2,404
African / African-American	0.0199%	5,017
Admixed American	0.0155%	6,466
European (non-Finnish)	0.0128%	7,832
Remaining individualsnot grpmax-eligible	0.00857%	11,669

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.Thr1142=
Coding: c.3426G>A
MANE Select: NM_182706
dbSNP: rs782309851
Type: single nucleotide variant
Location: chr8:143803560 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 1142: a β-strand; the pdz 4 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.Thr1142Met Likely benign ★ 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
SCRIB c.907-4C>G 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-thr1142 (accessed [today's date]).

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