Is SCRIB p.Ile5Val (c.13A>G) pathogenic?

SCRIB p.Ile5Val (c.13A>G) is classified Uncertain significance in SCRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: ambiguous (0.3795); Very rare (popmax 0.00389%, amr).

How common is SCRIB p.Ile5Val (c.13A>G) in the general population?

SCRIB p.Ile5Val (c.13A>G) is very rare (popmax 0.00389%, amr) (gnomAD).

What do computational predictors say about SCRIB p.Ile5Val (c.13A>G)?

AlphaMissense predicts ambiguous (score 0.3795) — an in-silico prediction, not a clinical call.

SCRIB p.Ile5Val

c.13A>G · rs748798089 · VCV3158665

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3795 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00389%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3795	ambiguous
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.24	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,447 bp · p 0.0026 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00389% Admixed American · 2/51,358 alleles

Filtering AF 0.000646% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000242%

Overall 0.000131% 2/1,524,874 alleles · very rare exomes 2/1,373,122 · genomes 0/151,752 · joint denominator

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.Ile5Val
Coding: c.13A>G
MANE Select: NM_182706
dbSNP: rs748798089
Type: single nucleotide variant
Location: chr8:143815360 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 5: the 'disordered' region; 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

Similar variants

SCRIB p.Ile5Leu Uncertain significance ★ ⚠ same residue
SCRIB c.3120+10C>G Benign/Likely benign ★★ same type
SCRIB c.504-9C>T Benign ★★ same type
SCRIB p.Ala1488= Likely benign ★★ same type
SCRIB p.Arg492= Benign ★★ same type
SCRIB p.Asn647= Benign/Likely benign ★★ same type
SCRIB p.Leu254= Benign ★★ same type
SCRIB p.Phe571= Benign ★★ same type

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-ile5val (accessed [today's date]).

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