Is SCRIB p.Gly194Arg (c.580G>A) pathogenic?

SCRIB p.Gly194Arg (c.580G>A) is classified Uncertain significance in SCRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: likely pathogenic (0.9931); No allele count reported in gnomAD v4.1 (AN 1,579,336).

How common is SCRIB p.Gly194Arg (c.580G>A) in the general population?

SCRIB p.Gly194Arg (c.580G>A) is no allele count reported in gnomAD v4.1 (AN 1,579,336) (gnomAD).

What do computational predictors say about SCRIB p.Gly194Arg (c.580G>A)?

AlphaMissense predicts likely pathogenic (score 0.9931) — an in-silico prediction, not a clinical call.

SCRIB p.Gly194Arg

c.580G>A · VCV4581387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9931 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,579,336)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9931	likely pathogenic · top 5% in SCRIB
REVEL	0.504	indeterminate
SaProt	LLR -15.73	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,447 bp · p 0.0026 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,579,336). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SCRIB
Protein: p.Gly194Arg
Coding: c.580G>A
MANE Select: NM_182706
Type: single nucleotide variant
Location: chr8:143813092 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 194: 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 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
SCRIB p.Pro1343= 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-gly194arg (accessed [today's date]).

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