Is STRADB p.Arg100Cys (c.298C>T) pathogenic?

STRADB p.Arg100Cys (c.298C>T) is classified Uncertain significance in STRADB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: likely benign (0.1434); Ultra-rare (popmax 0.0496%, mid).

How common is STRADB p.Arg100Cys (c.298C>T) in the general population?

STRADB p.Arg100Cys (c.298C>T) is ultra-rare (popmax 0.0496%, mid) (gnomAD).

What do computational predictors say about STRADB p.Arg100Cys (c.298C>T)?

AlphaMissense predicts likely benign (score 0.1434) — an in-silico prediction, not a clinical call.

STRADB p.Arg100Cys

c.298C>T · rs191184636 · VCV2324592

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1434 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1434	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Constraint at this position
Conservation	phyloP 5.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 25 kb · p 6e-11 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0496% Middle Eastern · 3/6,044 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.0126% 203/1,612,482 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0496%	2,015
East Asian	0.0312%	3,200
Remaining individualsnot grpmax-eligible	0.016%	6,245
African / African-American	0.0133%	7,491
European (non-Finnish)	0.0132%	7,561
South Asian	0.00662%	15,105
Admixed American	0.00503%	19,897
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,560

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: STRADB
Protein: p.Arg100Cys
Coding: c.298C>T
MANE Select: NM_018571
dbSNP: rs191184636
Type: single nucleotide variant
Location: chr2:201473059 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.39
Residue 100: the protein kinase domain

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

Similar variants

STRADB p.Arg100Leu Uncertain significance ★ ⚠ same residue
STRADB p.Ala103Pro Uncertain significance ★ ⚠ same type
STRADB p.Ala46Val Uncertain significance ★ ⚠ same type
STRADB p.Arg115Trp Uncertain significance ★ ⚠ same type
STRADB p.Arg329Gln Uncertain significance ★ ⚠ same type
STRADB p.Arg41Cys Uncertain significance ★ ⚠ same type
STRADB p.Asn163Ser Uncertain significance ★ ⚠ same type
STRADB p.Asp250Gly Uncertain significance ★ ⚠ 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/stradb-p-arg100cys (accessed [today's date]).

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