Is SCRIB p.Ala440Val (c.1319C>T) pathogenic?

SCRIB p.Ala440Val (c.1319C>T) is classified Benign in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-09). AlphaMissense: likely benign (0.0754); Low-frequency (popmax 1.25%, eas); Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Ala440Val (c.1319C>T)?

SCRIB p.Ala440Val (c.1319C>T) is associated with SCRIB-related disorder (ClinVar).

How common is SCRIB p.Ala440Val (c.1319C>T) in the general population?

SCRIB p.Ala440Val (c.1319C>T) is low-frequency (popmax 1.25%, eas) (gnomAD).

What do computational predictors say about SCRIB p.Ala440Val (c.1319C>T)?

AlphaMissense predicts likely benign (score 0.0754) — an in-silico prediction, not a clinical call.

SCRIB p.Ala440Val

c.1319C>T · rs79536435 · VCV3035741

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0754 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.25%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SCRIB-related disorder

Computational evidence

Protein change
AlphaMissense	0.0754	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -7.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP -0.98, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 20 kb · p 9.1e-08 · regional, not allelic
Overall
CADD	18.32	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 1.25% East Asian · 558/44,800 alleles

Filtering AF 1.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.13%

Overall 0.0361% 579/1,605,702 alleles · low-frequency exomes 531/1,453,376 · genomes 48/152,326 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.25%	80
Remaining individualsnot grpmax-eligible	0.0225%	4,451
South Asian	0.0033%	30,305
European (non-Finnish)	0.00034%	294,543

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.Ala440Val
Coding: c.1319C>T
MANE Select: NM_182706
dbSNP: rs79536435
Type: single nucleotide variant
Location: chr8:143810771 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 440: the 'sufficient for targeting to adherens junction and to inhibit cell proliferation' region; the 'disordered' 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-ala440val (accessed [today's date]).

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