Is SCRIB p.Arg1641Leu (c.4922G>T) pathogenic?

SCRIB p.Arg1641Leu (c.4922G>T) is classified Uncertain significance in SCRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: ambiguous (0.3682); No allele count reported in gnomAD v4.1 (AN 1,448,742).

How common is SCRIB p.Arg1641Leu (c.4922G>T) in the general population?

SCRIB p.Arg1641Leu (c.4922G>T) is no allele count reported in gnomAD v4.1 (AN 1,448,742) (gnomAD).

What do computational predictors say about SCRIB p.Arg1641Leu (c.4922G>T)?

AlphaMissense predicts ambiguous (score 0.3682) — an in-silico prediction, not a clinical call.

SCRIB p.Arg1641Leu

c.4922G>T · rs367850364 · VCV2474458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3682 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,448,742)

Computational evidence

Protein change
AlphaMissense	0.3682	ambiguous
REVEL	0.145	moderately benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 57 bp · p 0.011 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1616L vs ClinVar R1641L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,448,742). 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.Arg1641Leu
Coding: c.4922G>T
MANE Select: NM_182706
dbSNP: rs367850364
Type: single nucleotide variant
Location: chr8:143791209 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB

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

Similar variants

SCRIB p.Arg1641Cys 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-arg1641leu (accessed [today's date]).

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