Is STRADB p.Pro231Leu (c.692C>T) pathogenic?

STRADB p.Pro231Leu (c.692C>T) is classified Uncertain significance in STRADB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-27). AlphaMissense: ambiguous (0.5381); Very rare (popmax 0.0095%, nfe).

How common is STRADB p.Pro231Leu (c.692C>T) in the general population?

STRADB p.Pro231Leu (c.692C>T) is very rare (popmax 0.0095%, nfe) (gnomAD).

What do computational predictors say about STRADB p.Pro231Leu (c.692C>T)?

AlphaMissense predicts ambiguous (score 0.5381) — an in-silico prediction, not a clinical call.

STRADB p.Pro231Leu

c.692C>T · rs202088492 · VCV2384651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5381 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0095%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5381	ambiguous
REVEL	0.549	indeterminate
SaProt	LLR -10.02	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 25 kb · p 6e-11 · regional, not allelic
Overall
CADD	31.0	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 0.0095% European (non-Finnish) · 112/1,179,216 alleles

Filtering AF 0.00805% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00752%

Overall 0.00961% 155/1,613,084 alleles · very rare exomes 149/1,460,898 · genomes 6/152,186 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0344%	2,910
Remaining individualsnot grpmax-eligible	0.024%	4,163
European (non-Finnish)grpmax	0.0095%	10,529
Admixed American	0.00833%	11,998
South Asian	0.0011%	91,074

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro231Leu
Coding: c.692C>T
MANE Select: NM_018571
dbSNP: rs202088492
Type: single nucleotide variant
Location: chr2:201477762 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.39
Residue 231: the protein kinase domain

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.Arg41Cys Uncertain significance ★ ⚠ same type
STRADB p.Asn163Ser 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-pro231leu (accessed [today's date]).

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