Is SCRIB p.Val894Ile (c.2680G>A) pathogenic?

SCRIB p.Val894Ile (c.2680G>A) is classified Likely benign in SCRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: likely benign (0.0366); Very rare (popmax 0.0067%, afr).

How common is SCRIB p.Val894Ile (c.2680G>A) in the general population?

SCRIB p.Val894Ile (c.2680G>A) is very rare (popmax 0.0067%, afr) (gnomAD).

What do computational predictors say about SCRIB p.Val894Ile (c.2680G>A)?

AlphaMissense predicts likely benign (score 0.0366) — an in-silico prediction, not a clinical call.

SCRIB p.Val894Ile

c.2680G>A · rs781909065 · VCV2510941

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0366 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0366	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.22, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 20 kb · p 9.1e-08 · regional, not allelic
Overall
CADD	17.81	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 0.0067% African / African-American · 5/74,628 alleles

Filtering AF 0.00256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00192%

Overall 0.00277% 44/1,586,548 alleles · very rare exomes 38/1,434,422 · genomes 6/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0067%	14,926
Remaining individualsnot grpmax-eligible	0.00325%	30,770
European (non-Finnish)	0.00299%	33,424
South Asian	0.00228%	43,800

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.Val894Ile
Coding: c.2680G>A
MANE Select: NM_182706
dbSNP: rs781909065
Type: single nucleotide variant
Location: chr8:143805005 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 894: a β-strand; the pdz 2 domain; the 'interaction with arhgef7' region; the 'required for interaction with vim' region

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

Similar variants

SCRIB p.Val894Leu 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-val894ile (accessed [today's date]).

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