Is SCRIB p.Asp889= (c.2667T>C) pathogenic?

SCRIB p.Asp889= (c.2667T>C) is classified Likely benign in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-22). Rare (popmax 0.213%, nfe); Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Asp889= (c.2667T>C)?

SCRIB p.Asp889= (c.2667T>C) is associated with SCRIB-related disorder (ClinVar).

How common is SCRIB p.Asp889= (c.2667T>C) in the general population?

SCRIB p.Asp889= (c.2667T>C) is rare (popmax 0.213%, nfe) (gnomAD).

SCRIB p.Asp889=

c.2667T>C · rs200182640 · VCV3034132

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.213%, nfe)

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	all four deltas below 0.2 · A>C here scores Δ0.78 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.8	GERP -3.2
Overall
CADD	0.558	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.213% European (non-Finnish) · 2,498/1,172,734 alleles

Filtering AF 0.206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.203%

Overall 0.166% 2,662/1,599,040 alleles · rare exomes 2,522/1,446,802 · genomes 140/152,238 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.213%	469
Remaining individualsnot grpmax-eligible	0.105%	952
Finnishnot grpmax-eligible	0.0536%	1,864
African / African-American	0.0535%	1,870
Admixed American	0.0405%	2,468
Ashkenazi Jewishnot grpmax-eligible	0.00698%	14,326

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.Asp889=
Coding: c.2667T>C
MANE Select: NM_182706
dbSNP: rs200182640
Type: single nucleotide variant
Location: chr8:143805115 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 889: the pdz 2 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.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
SCRIB c.907-4C>T 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-asp889 (accessed [today's date]).

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