Is STRADB p.Arg41Cys (c.121C>T) pathogenic?

STRADB p.Arg41Cys (c.121C>T) is classified Uncertain significance in STRADB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: likely benign (0.0891); Ultra-rare (popmax 0.0802%, sas).

How common is STRADB p.Arg41Cys (c.121C>T) in the general population?

STRADB p.Arg41Cys (c.121C>T) is ultra-rare (popmax 0.0802%, sas) (gnomAD).

What do computational predictors say about STRADB p.Arg41Cys (c.121C>T)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

STRADB p.Arg41Cys

c.121C>T · rs565091574 · VCV3171580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0802%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -7.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.31 · evaluated, not missing
Pangolin	Δ0.21	loss · gain 0.01 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 1.8	GERP 1.1, phastCons 0.39
Regional constraint	o/e 0.70	unconstrained · MANE · 25 kb · p 6e-11 · regional, not allelic
Overall
CADD	17.65	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 0.0802% South Asian · 73/91,054 alleles

Filtering AF 0.0654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0599%

Overall 0.00527% 85/1,613,814 alleles · ultra-rare exomes 82/1,461,556 · genomes 3/152,258 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0802%	1,247
Remaining individualsnot grpmax-eligible	0.0096%	10,414
African / African-American	0.00133%	75,024
European (non-Finnish)	0.000424%	235,991

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.Arg41Cys
Coding: c.121C>T
MANE Select: NM_018571
dbSNP: rs565091574
Type: single nucleotide variant
Location: chr2:201469980 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.39

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

Similar variants

STRADB p.Ala103Pro Uncertain significance ★ ⚠ same type
STRADB p.Ala46Val Uncertain significance ★ ⚠ same type
STRADB p.Arg100Cys Uncertain significance ★ ⚠ same type
STRADB p.Arg100Leu Uncertain significance ★ ⚠ same type
STRADB p.Arg115Trp Uncertain significance ★ ⚠ same type
STRADB p.Arg329Gln 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-arg41cys (accessed [today's date]).

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