Is SCRIB p.Cys279= (c.837C>T) pathogenic?

SCRIB p.Cys279= (c.837C>T) is classified Likely benign in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-21). Rare (popmax 0.114%, eas); Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Cys279= (c.837C>T)?

SCRIB p.Cys279= (c.837C>T) is associated with SCRIB-related disorder (ClinVar).

How common is SCRIB p.Cys279= (c.837C>T) in the general population?

SCRIB p.Cys279= (c.837C>T) is rare (popmax 0.114%, eas) (gnomAD).

SCRIB p.Cys279=

c.837C>T · rs753383025 · VCV3057342

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.114%, eas)

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 -7.9	GERP -3.6
Overall
CADD	1.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.114% East Asian · 51/44,900 alleles

Filtering AF 0.0887% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0799%

Overall 0.00502% 81/1,613,562 alleles · rare exomes 76/1,461,404 · genomes 5/152,158 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.114%	880
Middle Eastern	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0096%	10,413
South Asian	0.0022%	45,539
European (non-Finnish)	0.0017%	58,986
African / African-American	0.00134%	74,906

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.Cys279=
Coding: c.837C>T
MANE Select: NM_182706
dbSNP: rs753383025
Type: single nucleotide variant
Location: chr8:143812335 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 279: 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

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-cys279 (accessed [today's date]).

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