Is SCRIB p.Val339= (c.1017C>T) pathogenic?

SCRIB p.Val339= (c.1017C>T) is classified Likely benign in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-17). Ultra-rare (popmax 0.0666%, afr); Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Val339= (c.1017C>T)?

SCRIB p.Val339= (c.1017C>T) is associated with SCRIB-related disorder (ClinVar).

How common is SCRIB p.Val339= (c.1017C>T) in the general population?

SCRIB p.Val339= (c.1017C>T) is ultra-rare (popmax 0.0666%, afr) (gnomAD).

SCRIB p.Val339=

c.1017C>T · rs779766623 · VCV3058268

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0666%, afr)

Conditions

SCRIB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3
Overall
CADD	0.704	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0666% African / African-American · 50/75,032 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0467%

Overall 0.00633% 102/1,611,250 alleles · ultra-rare exomes 68/1,458,908 · genomes 34/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0666%	1,501
Remaining individualsnot grpmax-eligible	0.00481%	20,784
European (non-Finnish)	0.00407%	24,569
East Asian	0.00223%	44,810

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.Val339=
Coding: c.1017C>T
MANE Select: NM_182706
dbSNP: rs779766623
Type: single nucleotide variant
Location: chr8:143811235 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 339: 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-val339 (accessed [today's date]).

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