Is SCRIB p.Asp1197= (c.3591C>T) pathogenic?

SCRIB p.Asp1197= (c.3591C>T) is classified Likely benign in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-21). Ultra-rare (popmax 0.0225%, sas); Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Asp1197= (c.3591C>T)?

SCRIB p.Asp1197= (c.3591C>T) is associated with SCRIB-related disorder (ClinVar).

How common is SCRIB p.Asp1197= (c.3591C>T) in the general population?

SCRIB p.Asp1197= (c.3591C>T) is ultra-rare (popmax 0.0225%, sas) (gnomAD).

SCRIB p.Asp1197=

c.3591C>T · VCV3354443

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0225%, sas)

Conditions

SCRIB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.2	GERP -3
Overall
CADD	0.983	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0225% South Asian · 20/89,036 alleles

Filtering AF 0.0148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00247% 39/1,579,888 alleles · ultra-rare exomes 32/1,427,582 · genomes 7/152,306 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0225%	4,452
African / African-American	0.0121%	8,280
Remaining individualsnot grpmax-eligible	0.00491%	20,385
East Asian	0.00228%	43,912
Admixed American	0.00171%	58,544
European (non-Finnish)	0.000429%	233,230

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.Asp1197=
Coding: c.3591C>T
MANE Select: NM_182706
Type: single nucleotide variant
Location: chr8:143803395 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 1197: the 'interaction with arhgef7' region

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

Disease context

SCRIB-related disorder

Similar variants

SCRIB p.Asp1197His 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
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-asp1197 (accessed [today's date]).

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